Q2 2024 Alnylam Pharmaceuticals Inc Earnings Call

August 1, 2024

Christine Lindenboom: Good day, and thank you for standing by. Welcome to the Alnylam Pharmaceuticals Q2 2024 Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a Q&A session. Please be advised that today's conference is being recorded. I would now like to hand the conference over to the company for their remarks. Please go ahead.

Operator: Good day, and thank you for standing by. Welcome to the Alnylam Pharmaceuticals Q2 2024 Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a Q&A session. Please be advised that today's conference is being recorded. I would now like to hand the conference over to the company for their remarks. Please go ahead.

Good day.

Speaker Change: And thank you for standing by. Welcome to the Alnylam Pharmaceuticals second quarter 2024 conference call.

Speaker Change: At this time, all participants are in a listen-only mode.

After the speaker's presentation, there will be a Q&A session. Please be advised that today's conference is being recorded.

Christine Lindenboom: Good morning. I'm Christine Lindenboom, Senior Vice President of Investor Relations and Corporate Communications at ALNYLAM. With me today are Yvonne Greenstreet, Chief Executive Officer, Tolga Tanguler, Chief Commercial Officer, Pushkal Garg, Chief Medical Officer, and Jeff Poulton, Chief Financial Officer. For those of you participating via conference call, the accompanying slides can be accessed by going to the Events section of the Investors page of our website, investors.alnylam.com/events. During today's call, as outlined in slide two, Yvonne will offer introductory remarks and provide some general context. Tolga will provide an update on our global commercial progress. Pushkal will review pipeline updates and clinical progress. And Jeff will review financials and guidance, followed by a summary of upcoming milestones before we open the call for your questions.

And I would now like to hand the conference over to the company for their remarks. Please go ahead. Good morning. I'm Christine Lindenboom, Senior Vice President of Investor Relations and Corporate Communications at Alnylam.

Speaker Change: With me today are Yvonne Greenstreet, Chief Executive Officer, Tolga Tanguler, Chief Commercial Officer, Pushkal Garg, Chief Medical Officer, and Jeff Poulton, Chief Financial Officer.

Christine Regan Lindenboom: For those of you participating via conference call, the accompanying slides can be accessed by going to the events section of the investors' page of our website, investors.alnylam.com/event. During today's call, as outlined in slide two, Yvonne will offer introductory remarks and provide some general context. [inaudible] will provide an update on our global commercial progress, [inaudible] will review pipeline updates and clinical progress and Jeff will review financial guidance followed by a summary of upcoming milestones before we open the call for your questions. I'd like to remind you that this call will contain opening remarks concerning Alnylam's future expectations and prospects which constitute forward-looking statements for the purposes of the Safe Harbor provision and Private Securities and Litigation Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent periodic report on file with the SEC.

Speaker Change: For those of you participating via conference call, the accompanying slides can be accessed by going to the events section of the investors page of our website, investors.alnylam.com slash events.

Speaker Change: During today's call, as outlined in slide 2, Yvonne will offer introductory remarks and provide some general context.

Christine Lindenboom: I would like to remind you that this call will contain remarks concerning Alnylam's future expectations, plans, and prospects, which constitute forward-looking statements for the purposes of the Safe Harbor Provision and the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent periodic report on file with the SEC. In addition, any forward-looking statements represent our views only as of the date of this recording and should not be relied upon as representing our views of any subsequent date. We specifically disclaim any obligation to update such statements. With that, I'd like to turn the call over to Yvonne. Yvonne?

I'd like to remind you that this call will contain opening remarks concerning Alnylam's future expectations and prospects which constitute forward-looking statements for the purposes of the Safe Harbor provision and Private Securities and Litigation Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent periodic report on file with the SEC.

Speaker Change: In addition, any forward-looking statements represent our views only of the date of this recording and should not be relied upon as representing our views of any subsequent date. We specifically disclaim any obligation to update such statements.

Christine Regan Lindenboom: In addition, any forward-looking statements represent our views only of the date of this reporting and should not be relied upon as representing our views of any subsequent date. We specifically disclaim any obligation to update such statements. With that, I'd like to turn the call over to Yvonne. Yvonne?

Yvonne L. Greenstreet: Thanks Christine and thank you everyone for joining the call today. The second quarter of 2024 was a transformative one for Alnylam. Commercially, we achieved 34% year-over-year growth in global net product revenue, generating $410 million in net product revenues, which was primarily driven by 37% year-over-year growth in our TTR business. And as such, we've raised our revenue guidance for the year by 11% as a midpoint. The commercial capability that we've established over the last five years will continue to drive significant growth for our current business and will be a key to our success as we prepare for a potential launch next year in the ATTR cardiomyopathy.

Yvonne Greenstreet: Thanks, Christine, and thank you, everyone, for joining the call today. Q2 2024 was a transformative one for ALNYLAM. Commercially, we achieved 34% year-over-year growth in global net product revenues, generating $410 million in net product revenues, which was primarily driven by 37% year-over-year growth in our TTR business. And as such, we've raised our revenue guidance for the year by 11% at the midpoint. The commercial capability that we've established over the last five years will continue to drive significant growth for our current business and will be a key to our success as we prepare for potential launch next year in ATTR cardiomyopathy.

Yvonne L. Greenstreet: To that end, the major highlight of Q2 was our announcement of positive top-line results from the Helios B Phase 3 study of VUTRISIRAN in ATTR cardiomyopathy, showing that the VUTRISIRAN improved cardiovascular outcomes, including a 35-36% mortality benefit compared to placebo and demonstrated encouraging safety. These results reflect the true power of the RNAi mechanism of action, supporting what we believe to be a highly differentiated therapeutic profile and positions VUTRISIRAN as the new standard of care in ATTR cardiomyopathy, assuming regulatory approval. Moreover, we believe these positive results can establish VUTRISIRAN as an anchor commercial franchise for Alnylam driving robust topline growth and value creation for many years to come. [inaudible] 25 goals, we are firm in our belief that we are on track to become a top tier biotech developing and commercializing transformative medicines for patients around the world with rare and prevalent diseases, driven by a high-yielding pipeline of first and or best-in-class product candidates from our organic product engine, all while delivering exceptional financial results. Before I turn it over to Tolga, I'm excited to tell you about a TTR Investor Day that we'll be hosting in New York City on Wednesday, October 9th. This event, which will be webcast live, will focus on our leadership in ATTR amyloidosis, including the efforts that we are undertaking to optimize the success of the launch of AMVUTTRA in ATTR cardiomyopathy. You'll hear from several of my Alnylam colleagues as well as external experts. We'll be sharing more details about this event shortly, and I hope that you can join us in New York on October the 9th.

To that end, the major highlight of Q2 was our announcement of positive top-line results from the Helios B Phase 3 study of VUTRISIRAN in ATTR cardiomyopathy, showing that the VUTRISIRAN improved cardiovascular outcomes, including a 35-36% mortality benefit compared to placebo and demonstrated encouraging safety. These results reflect the true power of the RNAi mechanism of action, supporting what we believe to be a highly differentiated therapeutic profile and positions VUTRISIRAN as the new standard of care in ATTR cardiomyopathy, assuming regulatory approval. Moreover, we believe these positive results can establish VUTRISIRAN as an anchor commercial franchise for Alnylam driving robust topline growth and value creation for many years to come. [inaudible] 25 goals, we are firm in our belief that we are on track to become a top tier biotech developing and commercializing transformative medicines for patients around the world with rare and prevalent diseases, driven by a high-yielding pipeline of first and or best-in-class product candidates from our organic product engine, all while delivering exceptional financial results.

Yvonne Greenstreet: To that end, the major highlight of Q2 was our announcement of positive top-line results from the HELIOS-B phase III study of vutrisiran in ATTR cardiomyopathy, showing that vutrisiran improved cardiovascular outcomes, including a 35% to 36% mortality benefit compared to placebo, and demonstrated encouraging safety. These results reflect the true power of the RNAi mechanism of action, supporting what we believe to be a highly differentiated therapeutic profile and position vutrisiran as the new standard of care in ATTR cardiomyopathy, assuming regulatory approval. Moreover, we believe these positive results can establish vutrisiran as an anchor commercial franchise for Alnylam, driving robust top-line growth and value creation for many years to come.

Yvonne: including a 35 to 36 percent mortality benefit compared to placebo and demonstrated encouraging safety.

Yvonne: and positioned Boutrisram as the new standard of care in ATTR cardiomyopathy, assuming regulatory approval.

Yvonne: Moreover, we believe these positive results can establish Futrisran as an anchor commercial franchise for Ireland, driving robust top-line growth and value creation for many years to come.

[inaudible] 25 goals, we are firm in our belief that we are on track to become a top tier biotech developing and commercializing transformative medicines for patients around the world with rare and prevalent diseases, driven by a high-yielding pipeline of first and or best-in-class product candidates from our organic product engine, all while delivering exceptional financial results.

Yvonne Greenstreet: With an eye towards our Alnylam P5x25 goals, we are firm in our belief that we are on track to become a top-tier biotech, developing and commercializing transformative medicines for patients around the world with rare and prevalent diseases, driven by a high-yielding pipeline of first and/or best-in-class product candidates from our organic product engine, all while delivering exceptional financial results. Before I turn it over to Tolga, I'm excited to tell you about a TTR investor day that we will be hosting in New York City on Wednesday, 9 October 2024. This event, which will be webcast live, will focus on our leadership in ATTR amyloidosis, including the efforts that we are undertaking to optimize the success of the launch of AMVUTTRA in ATTR cardiomyopathy. You'll hear from several of my Alnylam colleagues as well as external experts.

Speaker Change: developing and commercializing transformative medicine for patients around the world with rare and prevalent diseases driven by a high-yielding pipeline of first and or best-in-class product candidates from our organic product engine, all while delivering exceptional financial results.

Before I turn it over to Tolga, I'm excited to tell you about a TTR Investor Day that we'll be hosting in New York City on Wednesday, October 9th. This event, which will be webcast live, will focus on our leadership in ATTR amyloidosis, including the efforts that we are undertaking to optimize the success of the launch of AMVUTTRA in ATTR cardiomyopathy. You'll hear from several of my Alnylam colleagues as well as external experts. We'll be sharing more details about this event shortly, and I hope that you can join us in New York on October the 9th. With that, let me now turn the call over to Tolga for a review of our commercial performance. Tolga?

Yvonne Greenstreet: We'll be sharing more details about this event shortly, and I hope that you can join us in New York on 9 October 2024. With that, let me now turn the call over to Tolga for a review of our commercial performance. Tolga?

Speaker Change: You'll hear from several of my Alnylam colleagues as well as external experts.

Tolga Tanguler: With that, let me now turn the call over to Tolga for a review of our commercial performance. Tolga? Thanks Yvonne and good morning everyone. Q2 was another strong quarter for our commercial portfolio delivering net product sales growth of 34% across our portfolio compared with the second quarter of 2023 as we continue to increase the number of patients on therapy in both our TTR and rare franchises. Let me now turn to a summary of our second quarter TTR performance. Our TTR franchise achieved $307 million in global net product revenue, representing a 16% increase compared with the first quarter of 2024 and a 37% increase compared with the second quarter of 2023. This strong growth, now approaching six years from our initial commercial launch, supports our belief that there remains a significant opportunity for [inaudible]. We are approaching 5000 patients on treatment with ONPATTRO or AMVUTTRA globally. Still, a small percentage of the estimated tens of thousands of patients that suffer from this devastating disease. Now let me highlight the U.S. and rest of world [inaudible] performance. In the U.S, combined sales of ONPATTRO and AMVUTTRA increased by 16% compared with the first quarter and by a robust 40% year-over-year as momentum in new patient adds continue to drive strong growth. The U.S year over year growth was primarily driven by the following.

With that, let me now turn the call over to Tolga for a review of our commercial performance. Tolga?

Yvonne: With that, let me now turn the call over to Tolga for a review of our commercial performance. Tolga?

Tolga Tanguler: Thanks, Yvonne, and good morning, everyone. Q2 was another strong quarter for our commercial portfolio, delivering net product sales growth of 34% across our portfolio compared with the second quarter of 2023, as we continued to consistently increase the number of patients on therapy in both our TTR and rare franchises. Let me now turn to a summary of our second quarter TTR performance. Our TTR franchise achieved $307 million in global net product revenues, representing a 16% increase compared with the first quarter of 2024 and a 37% increase compared with the second quarter of 2023. This strong growth, now approaching six years from our initial commercial launch, supports our belief that there remains a significant opportunity in hATTR-PN. We are approaching 5,000 patients on treatment with ONPATTRO or AMVUTTRA globally, still a small percentage of the estimated tens of thousands of patients that suffer from this devastating disease.

Tolga Tanguler: Thanks Yvonne and good morning everyone. Q2 was another strong quarter for our commercial portfolio delivering net product sales growth of 34% across our portfolio compared with the second quarter of 2023 as we continue to increase the number of patients on therapy in both our TTR and rare franchises. Let me now turn to a summary of our second quarter TTR performance. Our TTR franchise achieved $307 million in global net product revenue, representing a 16% increase compared with the first quarter of 2024 and a 37% increase compared with the second quarter of 2023. This strong growth, now approaching six years from our initial commercial launch, supports our belief that there remains a significant opportunity for [inaudible]. We are approaching 5000 patients on treatment with ONPATTRO or AMVUTTRA globally. Still, a small percentage of the estimated tens of thousands of patients that suffer from this devastating disease. Now let me highlight the U.S. and rest of world [inaudible] performance. In the U.S, combined sales of ONPATTRO and AMVUTTRA increased by 16% compared with the first quarter and by a robust 40% year-over-year as momentum in new patient adds continue to drive strong growth. The U.S year over year growth was primarily driven by the following.

Tolga: Thanks, Yvonne, and good morning, everyone.

Tolga: Q2 was another strong quarter for our commercial portfolio, delivering net product sales growth of 34% across our portfolio compared with the second quarter of 2023.

Speaker Change: Let me now turn to a summary of our second quarter TTR performance.

Tolga Tanguler: Let me now turn to a summary of our second quarter TTR performance. Our TTR franchise achieved $307 million in global net product revenue, representing a 16% increase compared with the first quarter of 2024 and a 37% increase compared with the second quarter of 2023. This strong growth, now approaching six years from our initial commercial launch, supports our belief that there remains a significant opportunity for [inaudible]. We are approaching 5000 patients on treatment with ONPATTRO or AMVUTTRA globally. Still, a small percentage of the estimated tens of thousands of patients that suffer from this devastating disease.

Tolga: Our TTR franchise achieved $307 million in global net product revenues, representing a 16% increase compared with the first quarter of 2024, and a 37% increase compared with the second quarter of 2023.

Tolga: This strong growth, now approaching six years from our initial commercial launch, supports our belief that there remains a significant opportunity in HATTRPF.

Tolga: We are approaching 5,000 patients on treatment with Ompatra or Omutra globally, still a small percentage of the estimated tens of thousands of patients that suffer from this devastating disease.

Tolga Tanguler: Now, let me provide highlights of our U.S. and rest of the world hATTR-PN performance. In the U.S., combined sales of ONPATTRO and AMVUTTRA increased by 16% compared with the first quarter and by a robust 40% year-over-year as momentum in new patient adds continued to drive strong growth. The U.S. year-over-year growth was primarily driven by the following: a 34% increase in demand driven by the strength of our ongoing AMVUTTRA patient uptake, more than offsetting the decrease in patients on ONPATTRO that have switched to AMVUTTRA. It is worth noting that at the end of the Q2, approximately 90% of our U.S. TTR are on AMVUTTRA. Now, let me turn to our international markets, where the TTR franchise growth also increased by 16% compared with the first quarter and 35% year-over-year.

Tolga Tanguler: Now let me highlight the U.S. and rest of world [inaudible] performance. In the U.S, combined sales of ONPATTRO and AMVUTTRA increased by 16% compared with the first quarter and by a robust 40% year-over-year as momentum in new patient adds continue to drive strong growth. The U.S year over year growth was primarily driven by the following: a 34% increase in demand, driven by the strength of ongoing AMVUTTRA patient uptake, more than offsetting the decrease in patients on ONPATTRO that have switched to AMVUTTRA. It is worth noting that at the end of Q2, approximately 90% of our U.S. TTR are on AMVUTTRA.

Tolga: The U.S. year-over-year growth was primarily driven by the following, a 34% increase in demand, driven by the strength of ongoing Almutra patient uptake, more than offsetting the decrease in patients on Ompatra that have switched to Almutra.

Tolga: It is worth noting that at the end of the Q2, approximately 90% of our U.S. TTR are on ombud travel.

Tolga Tanguler: a 34% increase in demand, driven by the strength of ongoing AMVUTTRA patient uptake, more than offsetting the decrease in patients on ONPATTRO that have switched to AMVUTTRA. It is worth noting that at the end of Q2, approximately 90% of our U.S. TTR are on AMVUTTRA. Now let me turn to our international markets, where the TTR franchise growth also increased by 16% compared with the first quarter and 35% year over year.

a 34% increase in demand, driven by the strength of ongoing AMVUTTRA patient uptake, more than offsetting the decrease in patients on ONPATTRO that have switched to AMVUTTRA. It is worth noting that at the end of Q2, approximately 90% of our U.S. TTR are on AMVUTTRA.

Now let me turn to our international markets, where the TTR franchise growth also increased by 16% compared with the first quarter and 35% year over year. This strong year-over-year growth was primarily driven by increased demand for AMVUTTRA as patient uptake remained robust, including from our markets where we successfully launched AMVUTTRA in recent months. Finally, timing of orders in our partner markets, particularly Brazil, also contributed positively to the year-over-year growth.

Tolga Tanguler: The strong year-over-year growth was primarily driven by increased demand for AMVUTTRA as patient uptake remained robust, including from our markets where we successfully launched AMVUTTRA in recent months. Finally, timing of orders in our partner markets, particularly Brazil, also contributed positively to the year-over-year growth. As shared previously, our team is looking forward to bringing vutrisiran to patients with ATTR amyloidosis with cardiomyopathy, assuming successful regulatory review and approval. We believe we have a tremendous opportunity to transform the treatment paradigm based on the product profile and recent HELIOS-B results, combined with the significant unmet patient needs in ATTR amyloidosis with cardiomyopathy, which is an estimated tenfold larger prevalence than hATTR-PN, where AMVUTTRA is the market leader.

Tolga Tanguler: This strong year-over-year growth was primarily driven by increased demand for AMVUTTRA as patient uptake remained robust, including from our markets where we successfully launched AMVUTTRA in recent months. Finally, timing of orders in our partner markets, particularly Brazil, also contributed positively to the year-over-year growth. As shared previously, our team is looking forward to bringing VUTRISIRAN to patients with ATTR amyloidosis with cardiomyopathy, assuming successful regulatory review and approval.

This strong year-over-year growth was primarily driven by increased demand for AMVUTTRA as patient uptake remained robust, including from our markets where we successfully launched AMVUTTRA in recent months. Finally, timing of orders in our partner markets, particularly Brazil, also contributed positively to the year-over-year growth.

Tolga: The strong year-over-year growth was primarily driven by increased demand for Almutra, as patient uptake remained robust, including from our markets where we successfully launched Almutra in recent months.

As shared previously, our team is looking forward to bringing VUTRISIRAN to patients with ATTR amyloidosis with cardiomyopathy, assuming successful regulatory review and approval. We believe we have a tremendous opportunity to transform the treatment paradigm based on the product profile and recent Helios B results, combined with the significant unmet patient needs in ATTR amyloidosis with cardiomyopathy, which is an estimated tenfold larger prevalence than HAT-TRPN, where AMVUTTRA is the market leader. We believe VUTRISIRAN has the potential to address unmet patient needs and become the standard of care treatment for ATTR-CN with a first-line and market-leading profile in ATTR-CM, given its unique, highly differentiated mechanism of action, enabling rapid knockdown of TTR at the source that is deep and durable, reduction in mortality and CV hospitalization events, as well as substantial impact on measures of disease progression, an attractive quarterly dosing schedule with a site of care flexibility and favorable payer dynamics. We've been deeply committed to advancing treatment options in ATTR amyloidosis and understanding the unique needs of this community over the past decade and have built a strong foundation that will benefit our efforts to address the tremendous potential of ATTR-CM. At the same time, we recognize the critical importance of scaling our capabilities to establish VUTRISIRAN as the standard of care in ATTR-CM.

Yvonne L. Greenstreet: We believe we have a tremendous opportunity to transform the treatment paradigm based on the product profile and recent Helios B results, combined with the significant unmet patient needs in ATTR amyloidosis with cardiomyopathy, which is an estimated tenfold larger prevalence than HAT-TRPN, where AMVUTTRA is the market leader. We believe VUTRISIRAN has the potential to address unmet patient needs and become the standard of care treatment for ATTR-CN with a first-line and market-leading profile in ATTR-CN, given its unique, highly differentiated mechanism of action, enabling rapid knockdown of TTR at the source that is deep and durable.

Tolga: Combined with the significant unmet patient needs in ATTR amyloidosis with cardiomyopathy, which is an estimated tenfold larger prevalence than HATTRPN, where Ombudsray is the market leader.

Tolga Tanguler: We believe vutrisiran has the potential to address unmet patient needs and become the standard of care treatment of ATTR-CM with a first-line and market-leading profile in ATTR-CM, given its unique, highly differentiated mechanism of action, enabling rapid knockdown of TTR at the source that is deep and durable, reduction in mortality and severe hospitalization events, as well as substantial impact on measures of disease progression, an attractive quarterly dosing schedule with a site-of-care flexibility, and favorable payer dynamics. We've been deeply committed to advancing treatment options in ATTR amyloidosis and understanding the unique needs of this community over the past decade, and have built a strong foundation that will benefit our efforts to address the tremendous potential of ATTR-CM. At the same time, we recognize the critical importance of scaling our capabilities to establish vutrisiran as a standard of care in ATTR-CM.

Speaker Change: Unique Highly Differentiated Mechanism of Action, enabling rapid knockdown of TTR at the source that is deep and durable. Reduction in mortality and CV hospitalization events, as well as substantial impact on measures of disease progression.

Yvonne L. Greenstreet: reduction in mortality and CV hospitalization events, as well as substantial impact on measures of disease progression, an attractive quarterly dosing schedule with a site of care flexibility and favorable payer dynamics. We've been deeply committed to advancing treatment options in ATTR amyloidosis and understanding the unique needs of this community over the past decade and have built a strong foundation that will benefit our efforts to address the tremendous potential of ATTR-CM. At the same time, we recognize the critical importance of scaling our capabilities to establish VUTRISIRAN as the standard of care in ATTR-CM. To this end, we are advancing our launch preparation and expanding our capabilities, leveraging our strong foundation, including our deep and credible relation with TTR [inaudible], a global and highly specialized and integrated customer facility that delivers a seamless experience for patients and physicians, our track record of creating strong care and health system partnerships that supports exceptional patient access, not only in the U.S but also across all major global markets, including Canada, Europe, and Japan and our award-winning patient support service business that have enabled us to help patients access their online treatments quickly with one of the fastest timelines in the industry, transitioning from start form to therapy and also support patient adherence. We're also proud to have established a sustainable rare disease business that addresses a significant unmet need. The performance of [inaudible] and [inaudible] which delivered [inaudible] million dollars in global revenue combined product sales during the second quarter remained solid as we continue to increase our patient base. The rare disease franchise grew 2% versus the first quarter of 2024 and 25% compared with the second quarter of 2023. For [inaudible], product sales increased by 7% in Q2 compared with the second quarter of 2023 with the following regional highlights: a 17% in the U.S, primarily driven by growth in new patients on therapy and 8% in our rest of world market, primarily driven by the timing of orders in our partner market, which offset demand growth across European markets. For OXLUMO, we delivered a robust 68% year over year growth with the following regional dynamic:

reduction in mortality and CV hospitalization events, as well as substantial impact on measures of disease progression, an attractive quarterly dosing schedule with a site of care flexibility and favorable payer dynamics. We've been deeply committed to advancing treatment options in ATTR amyloidosis and understanding the unique needs of this community over the past decade and have built a strong foundation that will benefit our efforts to address the tremendous potential of ATTR-CM. At the same time, we recognize the critical importance of scaling our capabilities to establish VUTRISIRAN as the standard of care in ATTR-CM. To this end, we are advancing our launch preparation and expanding our capabilities, leveraging our strong foundation, including our deep and credible relation with TTR [inaudible], a global and highly specialized and integrated customer facility that delivers a seamless experience for patients and physicians, our track record of creating strong care and health system partnerships that supports exceptional patient access, not only in the U.S but also across all major global markets, including Canada, Europe, and Japan and our award-winning patient support service business that have enabled us to help patients access their online treatments quickly with one of the fastest timelines in the industry, transitioning from start form to therapy and also support patient adherence.

Tolga: An attractive quarterly dosing schedule with a site of care flexibility and favorable payer dynamics.

Speaker Change: We've been deeply committed to advancing treatment options in ATTR amyloidosis and understanding the unique needs of this community over the past decade and have built a strong foundation that will benefit our efforts to address the tremendous potential of ATTR-CM.

Tolga Tanguler: To this end, we are swiftly advancing our launch preparations and expanding our capabilities, leveraging our strong foundation, including our deep and credible relations with TTR centers, a global and highly specialized and integrated customer-facing team that delivers a seamless experience for patients and physicians, our track record of creating strong payer and health system partnerships that support exceptional patient access, not only in the US but also across all major global markets, including Canada, Europe, and Japan, and our award-winning patient support services team that have enabled us to help patients access their Alnylam treatments quickly with one of the fastest timelines in the industry, transitioning from start form to therapy, and also support patient adherence. We're also proud to have established a sustainable rare disease business that addresses a significant unmet patient need.

Speaker Change: To this end, we are seriously advancing our launch preparations and expanding our capabilities, leveraging our strong foundations, including our deep and credible relations with TTR sectors.

To this end, we are advancing our launch preparation and expanding our capabilities, leveraging our strong foundation, including our deep and credible relation with TTR [inaudible], a global and highly specialized and integrated customer facility that delivers a seamless experience for patients and physicians, our track record of creating strong care and health system partnerships that supports exceptional patient access, not only in the U.S but also across all major global markets, including Canada, Europe, and Japan and our award-winning patient support service business that have enabled us to help patients access their online treatments quickly with one of the fastest timelines in the industry, transitioning from start form to therapy and also support patient adherence.

Speaker Change: A global and highly specialized and integrated customer-facing team that delivers a seamless experience for patients and physicians.

Speaker Change: that have enabled us to help patients access their online treatments quickly with one of the fastest timelines in the industry transitioning from start form to therapy and also support patient adherence.

Tolga Tanguler: The performance of GIVLAARI and OXLUMO, which delivered $103 million in global revenues combined product sales during the second quarter, remains solid as we continue to increase our patient base. The rare disease franchise grew 2% versus the first quarter of 2024 and 25% compared with the second quarter of 2023. For GIVLAARI, product sales increased by 7% in Q2 compared with the second quarter of 2023, with the following regional highlights: a 17% increase in the US, primarily driven by growth in new patients on therapy; an 8% decrease in our rest of the world markets, primarily driven by the timing of orders in our partner markets, which offset demand growth across European markets.

Speaker Change: The rare disease franchise grew 2% versus the first quarter of 2024 and 25% compared with the second quarter of 2023.

We're also proud to have established a sustainable rare disease business that addresses a significant unmet need. The performance of [inaudible] and [inaudible] which delivered [inaudible] million dollars in global revenue combined product sales during the second quarter remained solid as we continue to increase our patient base. The rare disease franchise grew 2% versus the first quarter of 2024 and 25% compared with the second quarter of 2023. For [inaudible], product sales increased by 7% in Q2 compared with the second quarter of 2023 with the following regional highlights: a 17% in the U.S, primarily driven by growth in new patients on therapy and 8% in our rest of world market, primarily driven by the timing of orders in our partner market, which offset demand growth across European markets. For OXLUMO, we delivered a robust 68% year over year growth with the following regional dynamic: A 79% increase in the U.S, primarily driven by demand growth, a 61% growth from our rest of world market, driven by increase demand in both our European and partner markets. In conclusion, we delivered strong results in the second quarter and first half of the year with both our TTR and rare franchises delivering continued robust growth in patients on therapy and revenue. Accordingly, we're pleased to be operating our full year, net product revenue guidance today by 11% at the mid-point of our guidance range. Jeff will share more on that later. With that, I will now turn it over to Pushkal to review our recent R&D and pipeline progress. Pushkal?

Speaker Change: For Givlari, product sales increased by 7% in Q2, compared with the second quarter of 2023, with the following regional highlights.

Speaker Change: A 17% increase in U.S., primarily driven by growth in new patients on therapy. An 8% decrease in our rest of world markets, primarily driven by the timing of orders in our partner markets, which offset demand growth across European markets.

For [inaudible], product sales increased by 7% in Q2 compared with the second quarter of 2023 with the following regional highlights: a 17% in the U.S, primarily driven by growth in new patients on therapy and 8% in our rest of world market, primarily driven by the timing of orders in our partner market, which offset demand growth across European markets.

Tolga Tanguler: For OXLUMO, we delivered a robust 68% year-over-year growth with the following regional dynamics: a 79% increase in the US, primarily driven by demand growth; a 61% growth from our rest of the world markets, driven by increased demand in both our European and partner markets. In conclusion, we delivered strong results in the second quarter and first half of the year, with both our TTR and rare franchises delivering continued robust growth in patients on therapy and revenue. Accordingly, we're pleased to be upgrading our full-year net product revenue guidance today by 11% at the midpoint of our guidance range. Jeff will share on that more later. With that, I will now turn it over to Pushkal to review our recent R&D and pipeline progress. Pushkal?

For OXLUMO, we delivered a robust 68% year over year growth with the following regional dynamic: A 79% increase in the U.S, primarily driven by demand growth, a 61% growth from our rest of world market, driven by increase demand in both our European and partner markets. In conclusion, we delivered strong results in the second quarter and first half of the year with both our TTR and rare franchises delivering continued robust growth in patients on therapy and revenue.

Speaker Change: In conclusion, we delivered strong results in the second quarter and first half of the year with both our TTR and rare franchises delivering continuous robust growth in patients on therapy and revenue.

Speaker Change: Accordingly, we're pleased to be upgrading our full year Net Product Revenue Guidance today by 11% at the midpoint of our guidance range. Jeff will share on that more later.

Accordingly, we're pleased to be operating our full year, net product revenue guidance today by 11% at the mid-point of our guidance range. Jeff will share more on that later. With that, I will now turn it over to Pushkal to review our recent R&D and pipeline progress. Pushkal?

Speaker Change: With that, I will now turn it over to Pushkal to review our recent R&D and pipeline progress.

Pushkal Garg: Thanks Tolga, and good morning, everyone. As Yvonne highlighted in her introduction, the major highlight of the second quarter was our announcement of the exciting and overwhelmingly positive top line results from the Helios B Phase III study of VUTRISIRAN in patients with ATTR cardiomyopathy. With these results, we now have the first clinical trial data that demonstrates the ability of an RNAi therapeutic to improve cardiovascular outcomes.

Pushkal Garg: Thanks, Tolga, and good morning, everyone. As Yvonne highlighted in her introduction, the major highlight of the second quarter was our announcement of the exciting and overwhelmingly positive top-line results from the HELIOS-B phase III study of vutrisiran in patients with ATTR cardiomyopathy. With these results, we now have the first clinical trial data that demonstrate the ability of an RNAi therapeutic to improve cardiovascular outcomes. We observed truly outstanding results in this study, with vutrisiran meeting an extraordinarily high bar for efficacy, with statistical significance on all five prespecified primary and secondary endpoints in both of the study populations, highlighting the powerful impact of vutrisiran and its mechanism of action on this disease.

Pushkal: With these results, we now have the first clinical trial data that demonstrate the ability of an RNAi therapeutic to improve cardiovascular outcomes.

Yvonne L. Greenstreet: We observed truly outstanding results in this study, with VUTRISIRAN meeting an extraordinarily high bar for efficacy with statistical significance on all five pre-specified primary and secondary end points in both of the study populations, highlighting the powerful impact of VUTRISIRAN and its mechanism of action on this disease. Specifically, we observed 28 and 33% reduction in the risk of all cause mortality in the currency of the event and the overall and monotherapy populations respectively. And 36 and 35% reductions in all cause mortality in the overall and monotherapy populations respectively. These benefits were accompanied by clinically significant benefits on the six minute walk test, the KCCQ, and NYHA class, all of which are key measures of disease progression. We observed consistent effects in all key sub groups, including patients who are on baseline [inaudible]. And finally, VUTRISIRAN demonstrated encouraging safety and tolerability, consistent with its established profile. We're announcing this morning that the detailed results from the Helios B study will be presented as a hotline oral presentation at the European Society of Cardiology Congress on Friday, August 30th, 2024 in London. We will also host a conference call and webcast during the Congress to discuss these detailed results with investors. We're also hard at working with regulators as we work towards a supplemental NDA filing in the United States in late 2024 with additional global regulatory filings thereafter. As a reminder, we'll be using our priority review voucher to accelerate the U.S regulatory review in hopes of bringing this medicine to patients as quickly as possible. In addition to Helios B, we made progress across a number of other pipeline programs highlighting the breadth of opportunity we have with our RNAi platform. As we discussed in the last earnings call, we recently reported positive results from our Cardio-2 phase II study of ZILEBESIRAN, showing additive efficacy and good tolerability on top of standard care hypertensive and patients with inadequately controlled hypertension. Cardio-3 is now underway, evaluating ZILEBESIRAN on top of two or more agents in patients with high cardiovascular risk. And following that, we look forward to running a cardiovascular outcomes trial where our goal is to demonstrate the benefit of chronic blood pressure control in patients with high cardiovascular risk by showing reduction in cardiovascular mobility and mortality. We're also excited to have initiated dosing in the capricorn one phase II study of [inaudible], formally [inaudible] in patients with cerebral amyloid angiopathy. CAA is the second most common cause of inter cerebral hemorrage and remains highly under diagnosed with major unmet need. We've also advanced ALMKHK, which is in development for the treatment of type II diabetes with initiation of a part b phase of the phase one study. Our partners continue to make great progress as well. Sanofi submitted regulatory filings [inaudible] for patients with heamophilia in China, Brazil and the United States where the FDA has set a target action date of March 28, 2025. We've also announced today a pair of updates for our ongoing collaboration with Regeneron. First, we amended the license agreement for Semdiceran, an investigational RNAi therapeutic in development for the treatment of complement-mediated diseases, under which Regeneron gained exclusive rights to the asset as a monotherapy. In exchange, we received a $10 million upfront payment and are eligible to receive certain regulatory milestone and low double digit royalties on sale if approved. Additionally, as part of their regular portfolio review and prioritization efforts, Regeneron has decided to opt out for further codevelopment and co-commercialization of [inaudible]. As such, we now have full global development commercialization rights to [inaudible] in all indications. We're extremely excited about the potential of this program, our first in the CNS to address the unmet needs of patients in two significant disease areas: CAA, where we've just initiated a phase two study and Alzheimer's disease where we plan to start a phase two study at or around the end of the year. So in summary, we've made great progress in advancing our pipeline and platform with much more to come. As a reminder, we plan to file proprietary INDs for nine programs by the end of 2025 to get targets in the liver, CNS, muscle and adipose. As we include partner programs, we anticipate 15 new INDs by the end of 2025, representing a double for our clinical pipeline base by the end of next year. This remarkable and unique pace of innovation puts us in a great position to have a robust, self sustainable pipeline that can deliver meaningful impact to patients across multiple disease areas. With that, let me now turn it over to Jeff to review our financial results and upcoming milestones. Jeff?

We observed truly outstanding results in this study, with VUTRISIRAN meeting an extraordinarily high bar for efficacy with statistical significance on all five pre-specified primary and secondary end points in both of the study populations, highlighting the powerful impact of VUTRISIRAN and its mechanism of action on this disease. Specifically, we observed 28 and 33% reduction in the risk of all cause mortality in the currency of the event and the overall and monotherapy populations respectively. And 36 and 35% reductions in all cause mortality in the overall and monotherapy populations respectively. These benefits were accompanied by clinically significant benefits on the six minute walk test, the KCCQ, and NYHA class, all of which are key measures of disease progression. We observed consistent effects in all key sub groups, including patients who are on baseline [inaudible]. And finally, VUTRISIRAN demonstrated encouraging safety and tolerability, consistent with its established profile. We're announcing this morning that the detailed results from the Helios B study will be presented as a hotline oral presentation at the European Society of Cardiology Congress on Friday, August 30th, 2024 in London. We will also host a conference call and webcast during the Congress to discuss these detailed results with investors. We're also hard at working with regulators as we work towards a supplemental NDA filing in the United States in late 2024 with additional global regulatory filings thereafter. As a reminder, we'll be using our priority review voucher to accelerate the U.S regulatory review in hopes of bringing this medicine to patients as quickly as possible. In addition to Helios B, we made progress across a number of other pipeline programs highlighting the breadth of opportunity we have with our RNAi platform. As we discussed in the last earnings call, we recently reported positive results from our Cardio-2 phase II study of ZILEBESIRAN, showing additive efficacy and good tolerability on top of standard care hypertensive and patients with inadequately controlled hypertension. Cardio-3 is now underway, evaluating ZILEBESIRAN on top of two or more agents in patients with high cardiovascular risk. And following that, we look forward to running a cardiovascular outcomes trial where our goal is to demonstrate the benefit of chronic blood pressure control in patients with high cardiovascular risk by showing reduction in cardiovascular mobility and mortality. We're also excited to have initiated dosing in the capricorn one phase II study of [inaudible], formally [inaudible] in patients with cerebral amyloid angiopathy. CAA is the second most common cause of inter cerebral hemorrage and remains highly under diagnosed with major unmet need. We've also advanced ALMKHK, which is in development for the treatment of type II diabetes with initiation of a part b phase of the phase one study. Our partners continue to make great progress as well. Sanofi submitted regulatory filings [inaudible] for patients with heamophilia in China, Brazil and the United States where the FDA has set a target action date of March 28, 2025. We've also announced today a pair of updates for our ongoing collaboration with Regeneron. First, we amended the license agreement for Semdiceran, an investigational RNAi therapeutic in development for the treatment of complement-mediated diseases, under which Regeneron gained exclusive rights to the asset as a monotherapy. In exchange, we received a $10 million upfront payment and are eligible to receive certain regulatory milestone and low double digit royalties on sale if approved. Additionally, as part of their regular portfolio review and prioritization efforts, Regeneron has decided to opt out for further codevelopment and co-commercialization of [inaudible]. As such, we now have full global development commercialization rights to [inaudible] in all indications. We're extremely excited about the potential of this program, our first in the CNS to address the unmet needs of patients in two significant disease areas: CAA, where we've just initiated a phase two study and Alzheimer's disease where we plan to start a phase two study at or around the end of the year.

Speaker Change: We observed truly outstanding results in this study with Boutrice-Rand meeting an extraordinarily high bar for efficacy.

Pushkal Garg: Specifically, we observed 28% and 33% reductions in the risk of all-cause mortality and recurrent CV events in the overall and monotherapy populations, respectively, and 36% and 35% reductions in all-cause mortality in the overall and monotherapy populations, respectively. These outcome benefits were accompanied by clinically significant benefits on six-minute walk tests, KCCQ, and NYHA class, all of which are key measures of disease progression. We observed consistent effects in all key subgroups, including patients who were on baseline tafamidis. And finally, vutrisiran demonstrated encouraging safety and tolerability, consistent with its established profile. We're announcing this morning that the detailed results from the HELIOS-B study will be presented as a hotline oral presentation at the European Society of Cardiology Congress on Friday, 30 August 2024, in London. We will also host a conference call and webcast during the Congress to discuss these detailed results with investors.

Pushkal: Specifically, we observed 28 and 33 percent reductions in the risk of all-cause mortality and recurrent CV events in the overall and monotherapy populations, respectively.

Speaker Change: and 36 and 35 percent reductions in all-cause mortality in the overall and monotherapy populations respectively.

Speaker Change: These outcome benefits were accompanied by clinically significant benefits on 6-minute walk tests, KCCQ, and NYHA class, all of which are key measures of disease progression.

And finally, VUTRISIRAN demonstrated encouraging safety and tolerability, consistent with its established profile. We're announcing this morning that the detailed results from the Helios B study will be presented as a hotline oral presentation at the European Society of Cardiology Congress on Friday, August 30th, 2024 in London. We will also host a conference call and webcast during the Congress to discuss these detailed results with investors. We're also hard at working with regulators as we work towards a supplemental NDA filing in the United States in late 2024 with additional global regulatory filings thereafter. As a reminder, we'll be using our priority review voucher to accelerate the U.S regulatory review in hopes of bringing this medicine to patients as quickly as possible.

Speaker Change: We observe consistent effects in all E-subgroups, including patients who are on baseline defaminants.

Speaker Change: And finally, Utrish Srin demonstrated encouraging safety and tolerability, consistent with its established profile.

Speaker Change: We're announcing this morning that the detailed results from the Helios B study will be presented as a hotline oral presentation at the European Society of Cardiology Congress on Friday, August 30th, 2024 in London.

Pushkal Garg: We're also hard at work engaging with regulators as we work towards a supplemental NDA filing in the United States in late 2024, with additional global regulatory filings thereafter. As a reminder, we will be using our priority review voucher to accelerate the US regulatory review in hopes of bringing this medicine to patients as quickly as possible. In addition to HELIOS-B, we made progress across a number of other pipeline programs, highlighting the breadth of opportunity we have with our RNAi platform. As we discussed on the last earnings call, we recently reported positive results from our CARDIA-2 phase II study of zilebesiran, showing additive efficacy and good tolerability on top of standard-of-care antihypertensives in patients with inadequately controlled hypertension. CARDIA-3 is now underway, evaluating zilebesiran on top of two or more agents in patients who are at high cardiovascular risk.

In addition to Helios B, we made progress across a number of other pipeline programs highlighting the breadth of opportunity we have with our RNAi platform. As we discussed in the last earnings call, we recently reported positive results from our Cardio-2 phase II study of ZILEBESIRAN, showing additive efficacy and good tolerability on top of standard care hypertensive and patients with inadequately controlled hypertension.

Speaker Change: We're also hard at work engaging with regulators, as we work towards a supplemental NDA filing in the United States in late 2024, with additional global regulatory filings thereafter.

Speaker Change: As a reminder, we will be using our Priority Review Voucher to accelerate the U.S. Regulatory Review in hopes of bringing this medicine to patients as quickly as possible.

Cardio-3 is now underway, evaluating ZILEBESIRAN on top of two or more agents in patients with high cardiovascular risk. And following that, we look forward to running a cardiovascular outcomes trial where our goal is to demonstrate the benefit of chronic blood pressure control in patients with high cardiovascular risk by showing reduction in cardiovascular mobility and mortality. We're also excited to have initiated dosing in the capricorn one phase II study of [inaudible], formally [inaudible] in patients with cerebral amyloid angiopathy. CAA is the second most common cause of inter cerebral hemorrage and remains highly under diagnosed with major unmet need. We've also advanced ALMKHK, which is in development for the treatment of type II diabetes with initiation of a part b phase of the phase one study. Our partners continue to make great progress as well. Sanofi submitted regulatory filings [inaudible] for patients with heamophilia in China, Brazil and the United States where the FDA has set a target action date of March 28, 2025.

Speaker Change: In addition to Helios B, we made progress across a number of other pipeline programs, highlighting the breadth of opportunity we have with our RNAi platform.

Pushkal Garg: And following that, we look forward to running a cardiovascular outcomes trial, where our goal is to demonstrate the benefits of tonic blood pressure control in patients at high cardiovascular risk by showing reductions in cardiovascular morbidity and mortality. We're also excited to have initiated dosing in the CAPRICORN-1 phase II study of mivelsiran, formerly ALN-APP, in patients with cerebral amyloid angiopathy. CAA is the second most common cause of intracerebral hemorrhage and remains highly underdiagnosed, with major unmet need. We've also advanced ALN-KHK, which is in development for the treatment of Type 2 diabetes, with initiation of the Part B phase of the phase I study. Our partners continue to make great progress as well. Sanofi submitted regulatory filings for fitusiran for patients with hemophilia in China, Brazil, and the United States, where the FDA has set a target action date of 28 March 2025.

Speaker Change: And following that, we look forward to running a cardiovascular outcomes trial, where our goal is to demonstrate the benefits of tonic blood pressure control in patients at high cardiovascular risk by showing reductions in cardiovascular morbidity and mortality.

Speaker Change: We're also excited to have initiated dosing in the CAPRICORN1 Phase 2 study of Myvelseram, formerly AonNAPP, in patients with cerebral amyloid angiopathy.

Speaker Change: CAA is the second most common cause of intracerebral hemorrhage and remains highly underdiagnosed with major unmet need.

We've also announced today a pair of updates for our ongoing collaboration with Regeneron. First, we amended the license agreement for Semdiceran, an investigational RNAi therapeutic in development for the treatment of complement-mediated diseases, under which Regeneron gained exclusive rights to the asset as a monotherapy. In exchange, we received a $10 million upfront payment and are eligible to receive certain regulatory milestone and low double digit royalties on sale if approved.

Speaker Change: We've also advanced ALNKHK, which is in development for the treatment of type 2 diabetes with initiation of the Part B phase of the Phase 1 study.

Additionally, as part of their regular portfolio review and prioritization efforts, Regeneron has decided to opt out for further codevelopment and co-commercialization of [inaudible]. As such, we now have full global development commercialization rights to [inaudible] in all indications. We're extremely excited about the potential of this program, our first in the CNS to address the unmet needs of patients in two significant disease areas: CAA, where we've just initiated a phase two study and Alzheimer's disease where we plan to start a phase two study at or around the end of the year.

Pushkal Garg: We've also announced today a pair of updates to our ongoing collaboration with Regeneron. First, we amended the license agreement for cemdisiran, an investigational RNAi therapeutic in development for the treatment of complement-mediated diseases, under which Regeneron gained exclusive rights to the asset as a monotherapy. In exchange, we received a $10 million upfront payment and are eligible to receive certain regulatory milestones and low double-digit royalties on sales, if approved. Additionally, as part of their regular portfolio review and prioritization efforts, Regeneron has decided to opt out of further co-development and co-commercialization of mivelsiran. As such, we now have full global development and commercialization rights to mivelsiran in all indications.

Speaker Change: We've also announced today a pair of updates to our ongoing collaboration with Regeneron.

Speaker Change: First, we amended the License Agreement for Semdiceran, an investigational RNAi therapeutic in development for the treatment of complement-mediated diseases, under which Regeneron gained exclusive rights to the asset as a monotherapy.

Speaker Change: In exchange, we received a $10 million upfront payment and are eligible to receive certain regulatory milestones and low double-digit royalties on sales, if approved.

So in summary, we've made great progress in advancing our pipeline and platform with much more to come. As a reminder, we plan to file proprietary INDs for nine programs by the end of 2025 to get targets in the liver, CNS, muscle and adipose. As we include partner programs, we anticipate 15 new INDs by the end of 2025, representing a double for our clinical pipeline base by the end of next year. This remarkable and unique pace of innovation puts us in a great position to have a robust, self sustainable pipeline that can deliver meaningful impact to patients across multiple disease areas. With that, let me now turn it over to Jeff to review our financial results and upcoming milestones. Jeff?

Speaker Change: Additionally, as part of their regular portfolio review and prioritization efforts, Regeneron has decided to opt out of further co-development and co-commercialization of Myvel Saran.

Jeff Poulton: With that, let me now turn it over to Jeff to review our financial results and upcoming milestones. Jeff? Thanks Pushkal and good morning everyone. I'm pleased to be presenting a summary of Alnylam's Q2 2024 financial results and discussing our full year guidance.

With that, let me now turn it over to Jeff to review our financial results and upcoming milestones. Jeff?

Speaker Change: As such, we now have full global development and commercialization rights to MyBeltSaran in all indications.

Pushkal Garg: We're extremely excited about the potential of this program, our first in the CNS, to address the unmet needs of patients in two significant disease areas: CAA, where we've just initiated a phase II study, and Alzheimer's disease, where we plan to start a phase II study at or around the end of the year. So in sum, we've made great progress advancing our pipeline and platform, with much more to come. As a reminder, we plan to file proprietary INDs for 9 programs by the end of 2025 against targets in the liver, CNS, muscle, and adipose. If we include partnered programs, we anticipate 15 new INDs by the end of 2025, representing a doubling of our clinical pipeline by the end of next year.

Speaker Change: We're extremely excited about the potential of this program, our first in the CNS.

Speaker Change: to address the unmet needs of patients in two significant disease areas.

Speaker Change: CAA, where we've just initiated a phase 2 study, and Alzheimer's disease.

Speaker Change: So in sum, we've made great progress advancing our pipeline and platform, with much more to come.

Jeffrey Poulton: Thanks Pushkal and good morning everyone. I'm pleased to be presenting a summary of Alnylam's Q2 2024 financial results and discussing our full year guidance.

Speaker Change: As a reminder, we plan to file proprietary INDs for nine programs by the end of 2025 against targets in the liver, CNS, muscle, and adipose.

Pushkal Garg: This remarkable and unique pace of innovation puts us in a great position to have a robust, self-sustainable pipeline that can deliver meaningful impact to patients across multiple disease areas. With that, let me now turn it over to Jeff to review our financial results and upcoming milestones. Jeff?

Speaker Change: With that, let me now turn it over to Jeff to review our financial results and upcoming milestones. Jeff?

Jeff Poulton: Thanks, Pushkal, and good morning, everyone. I'm pleased to be presenting a summary of ALNYLAM's Q2 2024 financial results and discussing our full-year guidance. Starting with a summary of our P&L results for Q2 2024 compared with the same period in 2023. Total product revenue for the quarter was $410 million, or 34% growth versus 2023, with both our TTR and rare franchises reporting strong growth of 37% and 25%, respectively, primarily driven by continued strong demand, as Tolga previously highlighted. Net revenue from collaborations for the quarter was $227 million, representing a $221 million increase when compared with Q2 2023. The increase was primarily driven by the modification of our collaboration agreement with Regeneron, resulting in approximately $185 million of revenue, which was previously deferred. Royalty revenue for the quarter was $22 million, or more than three times what was recognized in the second quarter of 2023.

Jeff: Thanks Pushkal and good morning everyone. I'm pleased to be presenting a summary of Alnylam's Q2 2024 financial results and discussing our full year guidance.

Jeff Poulton: Starting with a summary of our P&L results for Q2 2024 compared with the same period in 2023. Total product revenue for the quarter was $410 million, or 34% growth versus 2023, with both our TTR and rare franchises reporting strong growth of 37% and 25%, respectively, primarily driven by continued strong demand, as Tolga previously highlighted. Net revenue from collaborations for the quarter was $227 million, representing a $221 million increase compared with Q2 of 2023. The increase was primarily driven by the modification of our collaboration agreement with Regeneron resulting in approximately $185 million of revenue which was previously deferred. Royalty revenue for the quarter was $22 million, or more than three times what was recognized in the second quarter of 2023.

Starting with a summary of our P&L results for Q2 2024 compared with the same period in 2023. Total product revenue for the quarter was $410 million, or 34% growth versus 2023, with both our TTR and rare franchises reporting strong growth of 37% and 25%, respectively, primarily driven by continued strong demand, as Tolga previously highlighted.

Jeff: Starting with a summary of our P&L results for Q2 2024 compared with the same period in 2023.

Jeff: Total product revenue for the quarter was $410 million or 34% growth versus 2023, with both our TTR and rare franchises reporting strong growth of 37% and 25% respectively, primarily driven by continued strong demand, as Tolga previously highlighted.

Net revenue from collaborations for the quarter was $227 million, representing a $221 million increase compared with Q2 of 2023. The increase was primarily driven by the modification of our collaboration agreement with Regeneron resulting in approximately $185 million of revenue which was previously deferred. Royalty revenue for the quarter was $22 million, or more than three times what was recognized in the second quarter of 2023.

Speaker Change: The increase was primarily driven by the modification of our collaboration agreement with Regeneron, resulting in approximately $185 million of revenue, which was previously deferred.

Christine Regan Lindenboom: The increase was driven by higher LEKVIO sales as Novartis continues to grow demand for LEKVIO worldwide. Gross margin on product sales was 84% for the quarter compared to 75% in the second quarter of 2023. Improvement in margin is primarily due to higher cost in 2023 associated with cancelled manufacturing commitments for ONPATTRO and other adjustments to inventory for which similar expenses were not realized in 2024. I expect our gross margin on product sales will be lower for the balance of the year driven by higher royalty state on AMVUTTRA as AMVUTTRA growth continues at a brisk pace. Our non-GAAP R&D expense has increased 14% in the second quarter compared to the same period in the prior year, primarily due to increased costs associated with our pre-clinical activities, increased development expenses associated with start up activities for the ZILEBESIRAN and [inaudible] studies and increased employee compensation expenses. Our non-GAAP SG&A expense increased 21% in the second quarter compared to the same period in the prior year primarily due to increased marketing investment associated with the promotion of our TTR therapy and increased employee compensation expenses. Our non-GAAP operating income for the quarter was 138 million, representing a 292 million improvement compared with Q2 2023, primarily driven by strong topline results, both in product sales as well as revenue from collaborations as previously highlighted. We ended the second quarter with cash, cash equivalents, and marketable securities of $2.6 billion, compared with $2.4 billion as of December 31st, 2023, with the increase primarily due to increased net product revenues and increased net proceeds from the issuance of common stock connection with employee stock option exercises. We continue to believe our current cash balance is sufficient to bridge us to a self-sustainable financial profile.

The increase was driven by higher LEKVIO sales as Novartis continues to grow demand for LEKVIO worldwide. Gross margin on product sales was 84% for the quarter compared to 75% in the second quarter of 2023. Improvement in margin is primarily due to higher cost in 2023 associated with cancelled manufacturing commitments for ONPATTRO and other adjustments to inventory for which similar expenses were not realized in 2024. I expect our gross margin on product sales will be lower for the balance of the year driven by higher royalty state on AMVUTTRA as AMVUTTRA growth continues at a brisk pace.

Jeff Poulton: The increase was driven by higher Leqvio sales as Novartis continues to grow demand for Leqvio worldwide. Gross margin on product sales was 84% for the quarter compared with 75% in Q2 2023. The improvement in margin is primarily due to higher costs in 2023 associated with canceled manufacturing commitments from ONPATTRO and other adjustments to inventory, for which similar expenses were not realized in 2024. I expect our gross margin on product sales will be lower for the balance of the year, driven by higher royalties paid on AMVUTTRA as AMVUTTRA growth continues at a brisk pace. Our non-GAAP R&D expenses increased 14% in Q2 compared to the same period in the prior year, primarily due to increased costs associated with our preclinical activities, increased development expenses associated with startup activities for the zilebesiran and mivelsiran clinical studies, and increased employee compensation expenses.

Speaker Change: Gross margin on product sales was 84% for the quarter, compared with 75% in the second quarter of 2023.

Speaker Change: The improvement in margin is primarily due to higher costs in 2023 associated with cancelled manufacturing commitments from Patro and other adjustments to inventory, for which similar expenses were not realized in 2024.

Speaker Change: I expect our gross margin on product sales will be lower for the balance of the year driven by higher royalties paid on Ambutra as Ambutra growth continues at a brisk pace.

Our non-GAAP R&D expense has increased 14% in the second quarter compared to the same period in the prior year, primarily due to increased costs associated with our pre-clinical activities, increased development expenses associated with start up activities for the ZILEBESIRAN and [inaudible] studies and increased employee compensation expenses. Our non-GAAP SG&A expense increased 21% in the second quarter compared to the same period in the prior year primarily due to increased marketing investment associated with the promotion of our TTR therapy and increased employee compensation expenses. Our non-GAAP operating income for the quarter was 138 million, representing a 292 million improvement compared with Q2 2023, primarily driven by strong topline results, both in product sales as well as revenue from collaborations as previously highlighted. We ended the second quarter with cash, cash equivalents, and marketable securities of $2.6 billion, compared with $2.4 billion as of December 31st, 2023, with the increase primarily due to increased net product revenues and increased net proceeds from the issuance of common stock connection with employee stock option exercises. We continue to believe our current cash balance is sufficient to bridge us to a self-sustainable financial profile.

Speaker Change: Our non-GAAP R&D expenses increased 14% in the second quarter compared to the same period in the prior year.

Jeff Poulton: Our non-GAAP SG&A expenses increased 21% in the second quarter compared to the same period in the prior year, primarily due to increased marketing investment associated with promotion of our TTR therapies and increased employee compensation expenses. Our non-GAAP operating income for the quarter was $138 million, representing a $292 million improvement compared with Q2 2023, primarily driven by strong top-line results, both in product sales as well as revenue from collaborations, as previously highlighted. We ended the second quarter with cash, cash equivalents, and marketable securities of $2.6 billion compared with $2.4 billion as of December 31, 2023, with the increase primarily due to increased net product revenues and increased net proceeds from the issuance of common stock in connection with employee stock option exercises. We continue to believe our current cash balance is sufficient to bridge us to a self-sustainable financial profile.

Our non-GAAP SG&A expense increased 21% in the second quarter compared to the same period in the prior year primarily due to increased marketing investment associated with the promotion of our TTR therapy and increased employee compensation expenses. Our non-GAAP operating income for the quarter was 138 million, representing a 292 million improvement compared with Q2 2023, primarily driven by strong topline results, both in product sales as well as revenue from collaborations as previously highlighted. We ended the second quarter with cash, cash equivalents, and marketable securities of $2.6 billion, compared with $2.4 billion as of December 31st, 2023, with the increase primarily due to increased net product revenues and increased net proceeds from the issuance of common stock connection with employee stock option exercises. We continue to believe our current cash balance is sufficient to bridge us to a self-sustainable financial profile.

Speaker Change: Our non-GAAP SG&A expenses increased 21% in the second quarter compared to the same period in the prior year, primarily due to increased marketing investment associated with promotion of our TTR therapies and increased employee compensation expenses.

Our non-GAAP operating income for the quarter was 138 million, representing a 292 million improvement compared with Q2 2023, primarily driven by strong topline results, both in product sales as well as revenue from collaborations as previously highlighted. We ended the second quarter with cash, cash equivalents, and marketable securities of $2.6 billion, compared with $2.4 billion as of December 31st, 2023, with the increase primarily due to increased net product revenues and increased net proceeds from the issuance of common stock connection with employee stock option exercises. We continue to believe our current cash balance is sufficient to bridge us to a self-sustainable financial profile.

Speaker Change: Our non-GAAP operating income for the quarter was $138 million, representing a $292 million improvement compared with Q2 2023, primarily driven by strong top-line results, both in product sales as well as revenue from collaborations, as previously highlighted.

Speaker Change: Compared with $2.4 billion as of December 31, 2023, with the increase primarily due to increased net product revenues and increased net proceeds from the issuance of common stock connection with employee stock option exercises.

Jeff Poulton: Now I'd like to turn to our 2024 guidance, where we are updating all components of our full-year guidance with the specific details as follows. We are increasing our net product revenue guidance from a range of $1.4 to 1.5 billion to a range of $1.575 to 1.65 billion, representing an 11% increase from the midpoint of the prior to the updated guidance. The primary driver of the increased guidance is the ongoing strength of performance in our hereditary ATTR polyneuropathy franchise. We are increasing our collaboration and royalty revenue guidance from a range of $325 to 425 million to a range of $575 to 650 million. The primary driver of the increase is the modification of our collaboration agreement with Regeneron, which resulted in the recognition of approximately $185 million of previously deferred revenue this quarter.

Christine Regan Lindenboom: Now I'd like to turn to our 2024 guidance, where we are updating all components of our full-year guidance with the specific details as follows. We are increasing our net product revenue guidance from a range of 1.4 to 1.5 billion to a range of 1.575 to 1.65 billion, representing an 11% increase from the mid-point of the prior to the updated guidance. The primary driver of the increased guidance is the ongoing strength of performance in our hereditary ATTR polyneuropathy franchise. We're increasing our collaboration in royalty revenue guidance from a range 325 to 425 million to a range of 575 to 650 million. The primary driver of the increase is the modification of our collaboration agreement with Regeneron which resulted in the recognition of approximately 185 million of previously deferred revenue this quarter. And lastly, we are increasing our guidance for combined non-GAAP R&D in SG&A expenses from a range of 1.675 to 1.775 billion to a range of 1.775 to 1.875 billion. There were two primary drivers of the increase. First, the opt out of [inaudible] by Regeneron will result in an increased R&D investment as the program is now wholly-owned by Alnylam. Second, given the strong Helios B top-line results, we are increasing our planned ATTR cardiomyopathy launch prep efforts to optimize our preparedness for an early 2025 launch in the US. Given the strong momentum in our business underpinning these guidance changes, along with the strength of the Helios B study results and our efforts to prepare for a highly successful ATTR cardiomyopathy launch next year, we are very confident in our ability to achieve both of the Alnylam [inaudible] by 25 financial goals that we established three and a half years ago, which include achieving a 40% plus compounded annual gross rate from total revenues across the five year period and achieving sustainable non-GAAP operating income within the period.

Now I'd like to turn to our 2024 guidance, where we are updating all components of our full-year guidance with the specific details as follows. We are increasing our net product revenue guidance from a range of 1.4 to 1.5 billion to a range of 1.575 to 1.65 billion, representing an 11% increase from the mid-point of the prior to the updated guidance. The primary driver of the increased guidance is the ongoing strength of performance in our hereditary ATTR polyneuropathy franchise.

Speaker Change: Now, I'd like to turn to our 2024 guidance where we are updating all components of our full year guidance with the specific details as follows.

Speaker Change: We are increasing our net product revenue guidance from a range of $1.4 to $1.5 billion to a range of $1.575 to $1.65 billion, representing an 11% increase from the midpoint of the prior to the updated guidance.

We're increasing our collaboration in royalty revenue guidance from a range 325 to 425 million to a range of 575 to 650 million. The primary driver of the increase is the modification of our collaboration agreement with Regeneron which resulted in the recognition of approximately 185 million of previously deferred revenue this quarter. And lastly, we are increasing our guidance for combined non-GAAP R&D in SG&A expenses from a range of 1.675 to 1.775 billion to a range of 1.775 to 1.875 billion. There were two primary drivers of the increase. First, the opt out of [inaudible] by Regeneron will result in an increased R&D investment as the program is now wholly-owned by Alnylam. Second, given the strong Helios B top-line results, we are increasing our planned ATTR cardiomyopathy launch prep efforts to optimize our preparedness for an early 2025 launch in the US. Given the strong momentum in our business underpinning these guidance changes, along with the strength of the Helios B study results and our efforts to prepare for a highly successful ATTR cardiomyopathy launch next year, we are very confident in our ability to achieve both of the Alnylam [inaudible] by 25 financial goals that we established three and a half years ago, which include achieving a 40% plus compounded annual gross rate from total revenues across the five year period and achieving sustainable non-GAAP operating income within the period.

And lastly, we are increasing our guidance for combined non-GAAP R&D in SG&A expenses from a range of 1.675 to 1.775 billion to a range of 1.775 to 1.875 billion. There were two primary drivers of the increase. First, the opt out of [inaudible] by Regeneron will result in an increased R&D investment as the program is now wholly-owned by Alnylam. Second, given the strong Helios B top-line results, we are increasing our planned ATTR cardiomyopathy launch prep efforts to optimize our preparedness for an early 2025 launch in the US. Given the strong momentum in our business underpinning these guidance changes, along with the strength of the Helios B study results and our efforts to prepare for a highly successful ATTR cardiomyopathy launch next year, we are very confident in our ability to achieve both of the Alnylam [inaudible] by 25 financial goals that we established three and a half years ago, which include achieving a 40% plus compounded annual gross rate from total revenues across the five year period and achieving sustainable non-GAAP operating income within the period.

Jeff Poulton: Lastly, we are increasing our guidance for combined non-GAAP R&D and SG&A expenses from a range of $1.675 to $1.775 billion to a range of $1.775 to $1.875 billion. There are two primary drivers of the increase. First, the opt-out of mivelsiran by Regeneron will result in increased R&D investment as the program is now wholly owned by Alnylam. Second, given the strong HELIOS-B top-line results, we are increasing our planned ATTR cardiomyopathy launch prep efforts to optimize our preparedness for an early 2025 launch in the US.

Speaker Change: Second, given the strong Heliospeed top-line results, we are increasing our planned ATTR cardiomyopathy launch prep efforts to optimize our preparedness for an early 2025 launch in the U.S.

Given the strong momentum in our business underpinning these guidance changes, along with the strength of the Helios B study results and our efforts to prepare for a highly successful ATTR cardiomyopathy launch next year, we are very confident in our ability to achieve both of the Alnylam [inaudible] by 25 financial goals that we established three and a half years ago, which include achieving a 40% plus compounded annual gross rate from total revenues across the five year period and achieving sustainable non-GAAP operating income within the period.

Jeff Poulton: Given the strong momentum in our business underpinning these guidance changes, along with the strength of the HELIOS-B study results and our efforts to prepare for a highly successful ATTR cardiomyopathy launch next year, we are very confident in our ability to achieve both of the Alnylam P5x25 financial goals that we established three and a half years ago, which include achieving a 40%+ compounded annual growth rate in total revenues across the five-year period and achieving sustainable non-GAAP operating income within the period. Let me now turn from financials and discuss some key goals and upcoming milestones slated for mid and late 2024. As was mentioned earlier, we will be presenting detailed results from HELIOS-B at the ESC Congress on Friday, 30 August 2024, in London. We will also be hosting a conference call and webcast to discuss the data.

Speaker Change: Given the strong momentum in our business underpinning these guidance changes,

Speaker Change: Along with the strength of the Helios B study results and our efforts to

Speaker Change: prepared for a highly successful ATTR cardiomyopathy launch next year. We were very confident in our ability to achieve both of the Alnylam P-to-the-fifth by 25 financial goals that we established.

Speaker Change: three and a half years ago, which include achieving a 40% plus compounded annual growth rate and total revenues across the five-year period and achieving sustainable non-GAAP operating income within the period.

Christine Regan Lindenboom: Let me now turn from the financials and discuss some key goals and upcoming milestones slated for mid and late 2024. As was mentioned earlier, we will be presenting detailed results from Helios B at the ESG Congress on Friday August 30th in London. We'll also be hosting a conference call and webcast to discuss the data. We've also announced today that we plan to host a TTR Investor Day on October 9th in New York City. At this event, we will feature senior leaders from Alnylam as well as external experts to highlight the potential of our TTR business. This will be webcast as well. We will be submitting a supplemental new drug application for VUTRISIRAN to the FDA using a priority review voucher. We plan to report interim results from part B of the phase I study of [inaudible] in patients with Alzheimer's disease. We expect three initiations by the end of 2024, including a phase III study of [inaudible] in patients with ATTR cardiomyopathy at or around year end, a phase II study from [inaudible] and patients with Alzheimer's disease at or around year end and a phase one study of [inaudible] in [inaudible] carcinoma. And we remain on track to file three investigational new drug applications by year end. Let me now turn it back to Christine to coordinate our Q&A session. Christine?

Let me now turn from the financials and discuss some key goals and upcoming milestones slated for mid and late 2024. As was mentioned earlier, we will be presenting detailed results from Helios B at the ESG Congress on Friday August 30th in London. We'll also be hosting a conference call and webcast to discuss the data. We've also announced today that we plan to host a TTR Investor Day on October 9th in New York City. At this event, we will feature senior leaders from Alnylam as well as external experts to highlight the potential of our TTR business. This will be webcast as well.

Speaker Change: As was mentioned earlier, we will be presenting detailed results from Helios B at the ESC Congress on Friday, August 30th in London. We will also be hosting a conference call and webcast to discuss the data.

Jeff Poulton: We've also announced today that we plan to host a TTR Investor Day on 9 October 2024 in New York City. At this event, we will feature senior leaders from Alnylam as well as external experts to highlight the potential of our TTR business. This will be webcast as well. We will be submitting a supplemental new drug application for vutrisiran to the FDA using a priority review voucher. We plan to report interim results from Part B of the phase I study of mivelsiran in patients with Alzheimer's disease. We expect 3 trial initiations by the end of 2024, including a phase III study of ALN-TTRsc04 in patients with ATTR cardiomyopathy at or around year-end, a phase II study for mivelsiran in patients with Alzheimer's disease at or around year-end, and a phase I study of ALN-BCAT and hepatocellular carcinoma.

Speaker Change: We've also announced today that we plan to host a TTR Investor Day on October 9th in New York City. At this event we will feature senior leaders from Alnylam as well as external experts to highlight the potential of our TTR business.

We will be submitting a supplemental new drug application for VUTRISIRAN to the FDA using a priority review voucher. We plan to report interim results from part B of the phase I study of [inaudible] in patients with Alzheimer's disease. We expect three initiations by the end of 2024, including a phase III study of [inaudible] in patients with ATTR cardiomyopathy at or around year end, a phase II study from [inaudible] and patients with Alzheimer's disease at or around year end and a phase one study of [inaudible] in [inaudible] carcinoma. And we remain on track to file three investigational new drug applications by year end. Let me now turn it back to Christine to coordinate our Q&A session. Christine?

Speaker Change: This will be webcast as well.

Speaker Change: We will be submitting a supplemental new drug application for Butresran to the FDA using a priority review voucher.

Speaker Change: We plan to report interim results from Part B of the Phase I study of Maldecyran in patients with Alzheimer's disease.

Speaker Change: We expect three trial initiations by the end of 2024, including a Phase III study of ALN-TTRF-C04 in patients with ATTR cardiomyopathy at or around year end.

Speaker Change: A Phase 2 Study for Mobile Saran in Patients with Alzheimer's Disease at or around year-end.

Jeff Poulton: We remain on track to file 3 investigational new drug applications by year-end. Let me now turn it back to Christine to coordinate our Q&A session. Christine?

Speaker Change: And we remain on track to file three investigational new drug applications by year-end.

Christine Regan Lindenboom: Thank you, Jeff. Operator, we will now open the call for your questions. To those dialled in, we would like to ask you to limit yourself to one question each and then get back in the queue if you have additional questions. At this time, if you would like to ask a question, please press the star and one on your telephone keypad. You may remove yourself from the queue at any time by pressing star two.

Christine Lindenboom: Thank you, Jeff. Operator, we will now open the call for your questions. To those dialed in, we would like to ask you to limit yourself to one question each and then get back in the queue if you have additional questions.

Speaker Change: Let me now turn it back to Christine to coordinate our Q&A session. Christine? Thank you, Jeff. Operator, we will now open the call for your questions. To those dialed in, we would like to ask you to limit yourself to one question each and then get back in the queue if you have additional questions.

Operator: At this time, if you would like to ask a question, please press the star and one on your telephone keypad. You may remove yourself from the queue at any time by pressing star two. Once again, that is star and one if you would like to ask a question. We'll take our first question from Ellie Merle with UBS. Your line is open.

Speaker Change: At this time, if you would like to ask a question, please press the star and 1 on your telephone keypad. You may remove yourself from the queue at any time by pressing star 2. Once again, that is star and 1 if you would like to ask a question. We'll take our first question from Ellie Merle with UBS. Your line is open.

Tolga Tanguler: Once again, that is star and one if you would like to ask a question. We'll take our first question from Ellie Merle with UBS. Your line is open. Hi, this is Jasmine on for Ellie. Thank you so much for taking our question. Can you discuss the reimbursement landscape in ATTR cardiomyopathy and how are you thinking about the potential difference [inaudible] between polyneuropathy and cardiomyopathy for AMVUTTRA? And how could the difference in medicare part C versus part D affect this especially given some of the IRA changes? Thank you. I think that's a question for you Tolga, maybe just to start off by emphasizing how pleased we are with the commercial performance to date and really see so much opportunity ahead of us both in polyneuropathy and that is the expanded label to include patients with cardiomyopathy assuming positive regulatory approval. Tolga, you may want to start with the big question. Yes, specific to the PN, I think it's actually a testament of the growth that we've been able to deliver this quarter and the prior quarters where patients get on therapy seamlessly thanks to our patient support services and preferable position that we have in terms of access. And patients actually stay on therapy and that, again, has a lot to do with our profile of the product and quarterly injectables, as well as our ability to continue to secure access for those patients.

Once again, that is star and one if you would like to ask a question. We'll take our first question from Ellie Merle with UBS. Your line is open. Hi, this is Jasmine on for Ellie. Thank you so much for taking our question. Can you discuss the reimbursement landscape in ATTR cardiomyopathy and how are you thinking about the potential difference [inaudible] between polyneuropathy and cardiomyopathy for AMVUTTRA? And how could the difference in medicare part C versus part D affect this especially given some of the IRA changes? Thank you.

Once again, that is star and one if you would like to ask a question. We'll take our first question from Ellie Merle with UBS. Your line is open.

[Analyst] (UBS Investment Bank): Hi, this is Jasmine on for Ellie. Thank you so much for taking our question. So can you discuss the reimbursement landscape in ATTR cardiomyopathy and how you're thinking about the potential difference in pricing between polyneuropathy and cardiomyopathy for AMVUTTRA, and how could the difference in Medicare Part B versus Part D affect this, especially given some of the IRA changes? Thank you.

Jasmine Fels: Hi, this is Jasmine on for Ellie. Thank you so much for taking our question. So can you discuss the reimbursement landscape in ATTR cardiomyopathy and how you're thinking about the potential difference in pricing between polyneuropathy and cardiomyopathy for AMVUTTRA, and how could the difference in Medicare Part B versus Part D affect this, especially given some of the IRA changes? Thank you.

Unknown: Hi, this is Jasmine on for Ellie. Thank you so much for taking our question. Can you discuss the reimbursement landscape in ATTR cardiomyopathy and how are you thinking about the potential difference [inaudible] between polyneuropathy and cardiomyopathy for AMVUTTRA? And how could the difference in medicare part C versus part D affect this especially given some of the IRA changes? Thank you.

Speaker Change: Hi, this is Jasmine on for Ellie. Thank you so much for taking our question.

Jasmine: So can you discuss the reimbursement landscape in ATTR cardiomyopathy, and how you're thinking about the potential difference in pricing between polyneuropathy and cardiomyopathy for in vitro, and how could the difference in Medicare Part B versus Part D affect this, especially given some of the IRA changes?

Yvonne Greenstreet: Yeah, I think that's a question for Tolga. Maybe just to start off by emphasizing how pleased we are with the commercial performance to date. How pleased we are with the commercial performance to date and really see so much opportunity ahead of us, both in polyneuropathy, and that as we expand the label to include patients with cardiomyopathy, assuming positive regulatory approval. But Tolga, you may want to respond to a specific question.

Speaker Change: I think that's a question for you Tolga, maybe just to start off by emphasizing how pleased we are with the commercial performance to date.

I think that's a question for you Tolga, maybe just to start off by emphasizing how pleased we are with the commercial performance to date and really see so much opportunity ahead of us both in polyneuropathy and that is the expanded label to include patients with cardiomyopathy assuming positive regulatory approval. Tolga, you may want to start with the big question. Yes, specific to the PN, I think it's actually a testament of the growth that we've been able to deliver this quarter and the prior quarters where patients get on therapy seamlessly thanks to our patient support services and preferable position that we have in terms of access. And patients actually stay on therapy and that, again, has a lot to do with our profile of the product and quarterly injectables, as well as our ability to continue to secure access for those patients.

Yvonne L. Greenstreet: I think that's a question for you Tolga, maybe just to start off by emphasizing how pleased we are with the commercial performance to date and really see so much opportunity ahead of us both in polyneuropathy and that is the expanded label to include patients with cardiomyopathy assuming positive regulatory approval. Tolga, you may want to start with the big question.

Speaker Change: How pleased we are with the commercial performance to date and really see so much opportunity ahead of us both in polyneuropathy and that as we...

Tolga Tanguler: Yeah, specific to the PN, I think it's actually a testament of the growth that we've been able to deliver this quarter and the prior quarters, where patients get on therapy seamlessly thanks to our patient support services and preferable position that we have in terms of our access, and patients actually stay on therapy. And that, again, has a lot to do with our profile of the product, quarterly injectables, and our ability to continue to secure access for those patients. When it comes to CM, we'll be leveraging a similar level of principles, meaning we will obviously make sure that patients have seamless access, and they stay on therapy without the burden of copay as little as possible.

Tolga Tanguler: Yes, specific to the PN, I think it's actually a testament of the growth that we've been able to deliver this quarter and the prior quarters where patients get on therapy seamlessly thanks to our patient support services and preferable position that we have in terms of access. And patients actually stay on therapy and that, again, has a lot to do with our profile of the product and quarterly injectables, as well as our ability to continue to secure access for those patients.

Speaker Change: this quarter and the prior quarters, where patients get on therapy seamlessly, thanks to our patient support services and preferable position that we have in terms of our access, and patients actually stay on therapy.

Tolga Tanguler: When it comes to CM, we'll be leveraging a similar level of principles, meaning we will obviously make sure that patients have seamless access and they stay on therapy without the burden of co-pays as little as possible. And given that we are actually physician-administered, which allows patients to be on Part B, we believe that is going to be a unique advantage compared to other available or future available products. Thanks Tolga. That's great. Next question, please.

When it comes to CM, we'll be leveraging a similar level of principles, meaning we will obviously make sure that patients have seamless access and they stay on therapy without the burden of co-pays as little as possible. And given that we are actually physician-administered, which allows patients to be on Part B, we believe that is going to be a unique advantage compared to other available or future available products.

Speaker Change: and they stay on therapy without the burden of co-pay as little as possible.

Tolga Tanguler: Given that we are actually physician-administered, which allows patients to be on Part B, we believe is going to be a unique advantage in compared to other available or future available products.

Speaker Change: And given that we are actually physician-administered, which allows patients to be on Part B, we believe is going to be a unique advantage compared to other available or future available products.

Pushkal Garg: Thanks, Tolga. That's great. Next question, please.

Christine Regan Lindenboom: Thanks Tolga. That's great. Next question, please.

Operator: Thank you. We'll take our next question from Kazin Amon with Bank of America. Your line is open. Hi, good morning. Thank you for taking my question. Mine is on VUTRISIRAN.

Operator: Thank you. We'll take our next question from Kazin Amon with Bank of America. Your line is open.

Operator: Thank you. We'll take our next question from Tazeen Aman with Bank of America. Your line is open.

Speaker Change: Thanks, Olga. That's great. Next question, please.

Kazin Amon: Hi, good morning. Thank you for taking my question. Mine is on VUTRISIRAN. And perhaps you can share feedback that you've gotten from physicians about their expectations for the use of the product and first line. Just based on the top line results from Helios B, which were impressive, it seems clear that there's definitely a market opportunity. I think investors would like to just get a better sense of what portion of that market could end up being first line and what kind of feedback you've gotten from physicians on that question. Thanks.

Unknown Executive: And perhaps you can share feedback that you've gotten from physicians about their expectations for the use of the product and first line. Just based on the top line results from Helios B, which were impressive, it seems clear that there's definitely a market opportunity. I think investors would like to just get a better sense of what portion of that market could end up being first line and what kind of feedback you've gotten from physicians on that question. Thanks. That's a great question. Clearly there is an unmet medical need here in this disease which is rapidly progressive and ultimately fatal. And we think we have a profile that's absolutely well set up to be standard of care. Tolga? Yeah, what we see with the physicians and we know this from other care payers as well, in any progressive debilitating, ultimately fatal disease, it really is imperative to start with the most potent treatment first. And given the topline Helios B results, we believe VUTRISIRAN is going to be well positioned to be the first signing. Look, at the end of the day, Helios B is the most contemporary cardiomyopathy study completed to date, and patients had [inaudible] backgrounds, backgrounds in [inaudible] against this incredibly high bar of contemporary backdrop which showed a profound impact. I don't know Pushkal if you want to add anything on this but I believe this is going to be a key driver in physicians leveraging their first line [inaudible]. Yeah, Tolga, I totally agree with everything you said. I think it's early days obviously but I think what we've heard repeatedly from physicians is that they are looking for an orthagonal mechanism of action that can have an impact on this disease. And the investigators and authors for the [inaudible] that we've shared the data with are incredibly excited, so we're looking forward to being able to roll those data out so we're seeing a lot of enthusiasm based on the data that we've shared so far. There's more to come at ESE and we look forward to that. Next question, please.

And perhaps you can share feedback that you've gotten from physicians about their expectations for the use of the product and first line. Just based on the top line results from Helios B, which were impressive, it seems clear that there's definitely a market opportunity. I think investors would like to just get a better sense of what portion of that market could end up being first line and what kind of feedback you've gotten from physicians on that question. Thanks. That's a great question. Clearly there is an unmet medical need here in this disease which is rapidly progressive and ultimately fatal. And we think we have a profile that's absolutely well set up to be standard of care. Tolga? Yeah, what we see with the physicians and we know this from other care payers as well, in any progressive debilitating, ultimately fatal disease, it really is imperative to start with the most potent treatment first. And given the topline Helios B results, we believe VUTRISIRAN is going to be well positioned to be the first signing. Look, at the end of the day, Helios B is the most contemporary cardiomyopathy study completed to date, and patients had [inaudible] backgrounds, backgrounds in [inaudible] against this incredibly high bar of contemporary backdrop which showed a profound impact. I don't know Pushkal if you want to add anything on this but I believe this is going to be a key driver in physicians leveraging their first line [inaudible]. Yeah, Tolga, I totally agree with everything you said. I think it's early days obviously but I think what we've heard repeatedly from physicians is that they are looking for an orthagonal mechanism of action that can have an impact on this disease. And the investigators and authors for the [inaudible] that we've shared the data with are incredibly excited, so we're looking forward to being able to roll those data out so we're seeing a lot of enthusiasm based on the data that we've shared so far.

[Analyst] (UBS Investment Bank): Hi, good morning. Thank you for taking my question. Mine is on vutrisiran, and perhaps you can share feedback that you've gotten from physicians about their expectations for use of the product and first line. Just based on the top-line results from HELIOS-B, which were impressive, it seems clear that there's definitely a market opportunity. I think investors would like to just get a better sense of what portion of that market could end up being first line and what kind of feedback you've gotten from physicians on that question. Thanks.

Tazeen Ahmad: Hi, good morning. Thank you for taking my question. Mine is on vutrisiran, and perhaps you can share feedback that you've gotten from physicians about their expectations for use of the product and first line. Just based on the top-line results from HELIOS-B, which were impressive, it seems clear that there's definitely a market opportunity. I think investors would like to just get a better sense of what portion of that market could end up being first line and what kind of feedback you've gotten from physicians on that question. Thanks.

Speaker Change: Hi, good morning. Thank you for taking my question. Mine is on dutriceran, and perhaps you can share feedback that you've gotten from physicians about their expectations for use of the product and first line

Yvonne Greenstreet: Yeah, no, that's a great question. And clearly, there is an unmet medical need here in this disease, which is rapidly progressive and ultimately fatal, and we think we have a profile that's absolutely well set up to be standard of care. Tolga?

Yvonne L. Greenstreet: That's a great question. Clearly there is an unmet medical need here in this disease which is rapidly progressive and ultimately fatal. And we think we have a profile that's absolutely well set up to be standard of care. Tolga?

Speaker Change: That's a great question. And, you know, clearly, there is a unmet medical need here in this, you know, disease, which is

Tolga Tanguler: Yeah, I mean, what we see with the physicians, and we know this from other therapy areas as well, in any progressive, debilitating, and essentially, ultimately, fatal disease, it really is imperative to start with the most potent treatment option first. And given the top-line HELIOS-B results, we believe vutrisiran is going to be well positioned to be the first-line agent. Look, I mean, at the end of the day, HELIOS-B is the most contemporary cardiomyopathy study completed to date, and patients had really aggressive backgrounds, background SGLT2s, tafamidis. And yet, against this incredibly high bar of contemporary backdrop, we showed a profound impact. I don't know, Pushkal, if you want to add anything else on this, but I believe this is going to be a key driver in physicians leveraging first-line treatment.

Tolga Tanguler: Yeah, what we see with the physicians and we know this from other care payers as well, in any progressive debilitating, ultimately fatal disease, it really is imperative to start with the most potent treatment first. And given the topline Helios B results, we believe VUTRISIRAN is going to be well positioned to be the first signing. Look, at the end of the day, Helios B is the most contemporary cardiomyopathy study completed to date, and patients had [inaudible] backgrounds, backgrounds in [inaudible] against this incredibly high bar of contemporary backdrop which showed a profound impact. I don't know Pushkal if you want to add anything on this but I believe this is going to be a key driver in physicians leveraging their first line [inaudible].

Speaker Change: and given the top-line Heliosphere results, we believe Wotwitschina is going to be well-positioned to be the first-line agent.

Speaker Change: Look, I mean, at the end of the day, Helios P is the most contemporary cardiomyopathy study completed to date.

Pushkal Garg: Yeah, Tolga, I totally agree with everything you said. I think it's early days obviously but I think what we've heard repeatedly from physicians is that they are looking for an orthagonal mechanism of action that can have an impact on this disease. And the investigators and authors for the [inaudible] that we've shared the data with are incredibly excited, so we're looking forward to being able to roll those data out so we're seeing a lot of enthusiasm based on the data that we've shared so far.

Pushkal Garg: Yeah, I think building Tolga, I totally agree with everything you said, and I think, Tazeen, it's early days, obviously, but I think what we've heard repeatedly from clinicians is that they're looking for an orthogonal mechanism of action that can have an impact on this disease. And the investigators and authors for the ESC presentation center that we've shared the data deeply with are incredibly excited. And so we're looking forward to being able to roll those data out, but I think we're seeing a lot of enthusiasm based on the data that we've shared so far. And of course, more to come at ESC, and we look forward to that. Next question, please.

Speaker Change: and you know the investigators and authors for the ESC presentation center that we've shared the data deeply with are incredibly excited and so we're looking forward to being able to roll those data out but I think we're seeing a lot of enthusiasm based on the data that we've shared so far.

Yvonne L. Greenstreet: There's more to come at ESC and we look forward to that. Next question, please.

Operator: Thank you. We'll take our next question from Maury Raycroft with Jeffreys. Please go ahead. Your line is open. Hi, good morning. Thanks for taking my question. I'll ask about ESE for the upcoming data. I'm just wondering if you'll report [inaudible] and time [inaudible] with the different mono versus combo sub groups in the study or maybe talk more about what kinds of details you might disclose at the conference. That's a great question, Maury, and clearly we're working on finalizing the details as we speak. Pushkal?

Operator: Thank you. We'll take our next question from Maury Raycroft with Jeffreys. Please go ahead. Your line is open.

Operator: Thank you. We'll take our next question from Maury Rycroft with Jefferies. Please go ahead. Your line is open.

Speaker Change: Thank you. We'll take our next question from Maury Raycroft with Jeffreys. Please go ahead. Your line is open.

Maury Raycroft: Hi, good morning. Thanks for taking my question. I'll ask about ESC for the upcoming data. I'm just wondering if you'll report [inaudible] and time [inaudible] with the different mono versus combo sub groups in the study or maybe talk more about what kinds of details you might disclose at the conference.

[Analyst] (BMO Capital Markets): Hi, good morning. Congrats on the quarter, and thanks for taking my question. I'll ask about ESC for the upcoming data. I'm wondering if you'll report KM curves and time-to-events kinetics for the different mono versus combo subgroups in the study, or maybe talk more about what types of details you plan to disclose at the conference.

Maury Raycroft: Hi, good morning. Congrats on the quarter, and thanks for taking my question. I'll ask about ESC for the upcoming data. I'm wondering if you'll report KM curves and time-to-events kinetics for the different mono versus combo subgroups in the study, or maybe talk more about what types of details you plan to disclose at the conference.

Yvonne L. Greenstreet: That's a great question, Maury, and clearly we're working on finalizing the details as we speak. Pushkal?

Yvonne Greenstreet: Yeah, that's a great question, Maury. Clearly, we're working on finalizing the details as we speak. Pushkal?

Pushkal: And that's a great question, Maury, and clearly we're working on finalizing the details as we speak. Pushkal. Yeah, thanks, Maury. Look, we are working with the investigators and authors to sort of finalize the content.

Pushkal Garg: Yeah, thanks, Maury. Look, we are working with the investigators and authors to sort of finalize the content but we plan to go into pretty extensive detail on the endpoints in the study and the results that we presented at the top line. If you think we're really excited to be able to share that now broadly with the community, both the clinical community and the investor community. So I anticipate this will include baseline characteristics. You'll hear about sort of how this is a very contemporary population of patients that were heavily treated with other medications, effective agents. You'll see the results of the primary endpoint, including the components and all the secondaries and we'll also be sharing curves for the primary endpoint and the secondary endpoint of all-cause mortality. And you'll see the consistency of effect across a variety of subgroups. And specifically, we'll be sharing some curves in the overall and based on baseline [inaudible]. So I think you'll get a pretty wholesome view of the results. And, of course, we'll have other opportunities to dive deeper into data at HFSA. But we're limited in how much we can present at ESE, and there's a lot of rich data coming out of this incredible clinical trial that we'll be sharing in the weeks to come.

Pushkal Garg: Yeah, thanks, Maury. Look, we are working with the investigators and authors to sort of finalize the content. But we plan to go into pretty expansive detail on the endpoints in the study and the results that we presented at the top line. I think we're really excited to be able to share that now broadly with the community, both the clinical community and the investor community. So this will include, I anticipate, baseline characteristics. You'll hear about sort of how this is a very contemporary population of patients that was heavily treated with other medications, effective agents. You'll see the results on the primary endpoint, including the components and all the secondaries. And we'll also be sharing curves for the primary endpoint and secondary endpoint of all-cause mortality.

Pushkal: but we plan to go into pretty expansive detail on the end points in the study.

Speaker Change: And the results will be presented at the top line if you think we're really excited to be able to share that now broadly with the community, both the clinical community and the investor community. So this will include, you know, I anticipate this will include baseline characteristics.

Pushkal Garg: You'll hear about sort of how this is a very contemporary population of patients that were heavily treated with other medications, effective agents. You'll see the results of the primary endpoint, including the components and all the secondaries

Pushkal Garg: and we'll also be sharing curves for the primary endpoint and the secondary endpoint of all-cause mortality. And you'll see the consistency of effect across a variety of subgroups. And specifically, we'll be sharing some curves in the overall and based on baseline [inaudible]. So I think you'll get a pretty wholesome view of the results. And, of course, we'll have other opportunities to dive deeper into data at HFSA. But we're limited in how much we can present at ESE, and there's a lot of rich data coming out of this incredible clinical trial that we'll be sharing in the weeks to come. Thanks Pushkal. Next question.

and we'll also be sharing curves for the primary endpoint and the secondary endpoint of all-cause mortality. And you'll see the consistency of effect across a variety of subgroups. And specifically, we'll be sharing some curves in the overall and based on baseline [inaudible]. So I think you'll get a pretty wholesome view of the results. And, of course, we'll have other opportunities to dive deeper into data at HFSA. But we're limited in how much we can present at ESE, and there's a lot of rich data coming out of this incredible clinical trial that we'll be sharing in the weeks to come.

Speaker Change: and all the secondaries. And we'll also be sharing curves for the primary endpoint and secondary endpoint of all-cause mortality. And you'll see that across.

Pushkal Garg: And you'll see that across the key, you'll see the consistency of effect across a variety of subgroups, and specifically, we'll be sharing some curves in the overall and based on baseline tafamidis. So I think you'll get a pretty fulsome view of the results. And of course, we'll have other opportunities to dive deeper into data at HFSA. We're limited in how much we can present at ESC, and there's a lot of rich data coming out of this incredible clinical trial that we'll be sharing in the weeks to come. Thanks, Pushkal. Next question?

Yvonne L. Greenstreet: Thanks Pushkal. Next question.

Christine Regan Lindenboom: Thank you. We'll take our next question from Paul Matias with Stifel. Your line is open. Hey, thanks so much for taking our question. This is Julian Pino on for Paul. I was just wondering, with respect to the ALN APP program, can you provide a little bit more color on what the potential phase two design could look like in Alzheimer's and what endpoints you'll be looking at? And then further, I didn't see anything, unless I missed it, on the HBME obesity program. Is that still ongoing? And I'm curious about the status of that as well. Thank you.

Operator: Thank you. We'll take our next question from Paul Matias with Stifel. Your line is open.

Operator: Thank you. We'll take our next question from Paul Matthias with Stifel. Your line is open.

Pushkal: Thanks Pushkal. Next question?

Unknown Executive: I was just wondering, with respect to the ALN APP program, can you provide a little bit more color on what the potential phase two design could look like in Alzheimer's and what endpoints you'll be looking at? And then further, I didn't see anything, unless I missed it, on the HBME obesity program. Is that still ongoing?

[Analyst] (Jefferies LLC): Hey, thanks so much for taking our question. This is Julian Pino on for Paul. I was just wondering, with respect to the ALN-APP program, can you provide a little bit more color on what the potential Phase II design could look like in Alzheimer's and what endpoints you'll be looking at? And then further, I didn't see anything unless I missed it on the HBME obesity program. Is that still ongoing? And I'm curious the status of that as well. Thank you.

Julian Pino: Hey, thanks so much for taking our question. This is Julian Pino on for Paul. I was just wondering, with respect to the ALN-APP program, can you provide a little bit more color on what the potential Phase II design could look like in Alzheimer's and what endpoints you'll be looking at? And then further, I didn't see anything unless I missed it on the HBME obesity program. Is that still ongoing? And I'm curious the status of that as well. Thank you.

Speaker Change: Hey, thanks so much for taking our question. This is Julian Pino on for Paul.

Julian Pino: Hey, thanks so much for taking our question. This is Julian Pino on for Paul. I was just wondering, with respect to the ALN APP program, can you provide a little bit more color on what the potential phase two design could look like in Alzheimer's and what endpoints you'll be looking at? And then further, I didn't see anything, unless I missed it, on the HBME obesity program. Is that still ongoing? And I'm curious about the status of that as well. Thank you.

Julian Pino: and what endpoints you'll be looking at. And then further didn't see anything unless I missed it on the HBNE obesity program. Is that still ongoing? And I'm curious the status of that as well. Thank you.

Yvonne Greenstreet: Yeah, no. Look, we're delighted with the progress of the ALN-APP program, now known as mivelsiran. I can't pronounce it, actually, Pushkal. But it's advancing well. We've been able to demonstrate rapid, robust, and sustained reductions in SAPP alpha and beta, and going very well. And we feel there's tremendous potential in the two indications that we are progressing, both Alzheimer's disease and cerebral amyloid angiopathy. Pushkal, maybe talk a little bit about where we're looking at the future.

Speaker Change: PR Noah. Look, we're delighted with the progress of the LNATC program, now known as my views. I can't pronounce it, actually, Pushkal.

Speaker Change: Reductions in SAP Pialpha and Beta

Speaker Change: You know, going very well, and we feel there's tremendous potential in the two indications that we are progressing.

Pushkal Garg: Absolutely. So taking your two questions and building on what Yvonne said, look, APP, very exciting program. We just presented some data at AAIC, actually, that showed that we had consistent knockdown in both soluble APP alpha and beta, but also the downstream disease-related biomarkers of Aβ 40 and 42 that are involved in CAA and Alzheimer's disease, and continue to see very encouraging safety coming out of that program as well. So that program remains on track. We're very excited. As we talked about, we've recently kicked off a study in cerebral amyloid angiopathy, which is like a second leading cause of hemorrhage. And as you noted, we will be starting a study in Alzheimer's disease as well. We aren't ready to talk about the specifics of that. We're obviously working through our trial design, but we'll share that with you shortly.

Speaker Change: Just like technically the cause of hemorrhage.

Speaker Change: And as you noted, we will be starting a study in Alzheimer's disease as well. We aren't ready to talk about the specifics of that. We're obviously working through our trial design, but we'll share that with you shortly. But we're very encouraged about this upstream mechanism, its potential to be very differentiated in this disease space and hopefully have a favorable impact on the disease of Alzheimer's disease, which we all know has a tremendous burden.

Pushkal Garg: But we're very encouraged about this upstream mechanism. It's potential to be very differentiated in this disease space and hopefully have a favorable impact on the disease of Alzheimer's disease, which I think we all know has a tremendous burden. With regard to your second question on inhibin-E, look, I don't think there's any really specific updates I want to give on the early preclinical programs other than to say what you heard in the main comments was just we are pushing very aggressively in terms of our 225 strategy to move a multitude of programs forward based on the excitement that we have around the platform here. And so we are on track for three-plus INDs this year, nine proprietary INDs by the end of 2025, and a doubling of our pipeline by the end of next year.

Speaker Change: The excitement that we have around the platform.

Speaker Change: 9 proprietary INDs by the end of 2025.

Pushkal Garg: But we'll give updates on those specific programs in due course and keep you posted. Perfect, Pushkal. Next question.

Unknown Executive: Yeah, look, we're delighted with the progress of ATT program. [inaudible], it's advancing well, we've been able to demonstrate rapid and robust reductions in SAPPR data. It's going very well and we feel there's tremendous potential in the two indications that we are progressing for Alzheimer's disease and [inaudible] amyloid angiopathy. Pushkal, maybe talk a little bit about what we're looking at for the future. Absolutely. So taking your two questions and building on what Yvonne said, ATT is a very exciting program. We presented some data at AIC actually that showed that we had consistent knockdown in both [inaudible] alpha and beta but also the downstream disease related biomarkers [inaudible] 40 and 42 that are involved in CAA and Alzheimer's disease and continue to see very encouraging safety coming out of that program as well. So that program remains on track. We're very excited. As we've talked about, we recently kicked off the study in [inaudible] amyloid angiopathy, the second leading cause of hemorrhage. As you noted, we will be starting a study in Alzheimer's disease as well. We aren't ready to talk about the specifics of that. We're obviously working through our trial design but we'll share that with you shortly but we're very encouraged about this upstream mechanism. Its potential to be very differentiated in the disease space and hopefully have a favorable impact on the disease of Alzheimer's, which we all know adds a tremendous burden. With regard to your second question on [inaudible], look, I don't think there are any specific updates I want to give on the early pre-clinical programs other than to say what you heard in the main comments was just we are pushing very aggressively in terms of our 225 strategy to move a multitude of programs forward based on the excitement that we have around the platform here. And so we are on track for 3 plus INDs this year, 9 proprietary INDs by the end of '25 and a doubling of our pipeline by the end of next year. But we will give updates on those specific programs in due course and keep you posted. Next question. Thank you. We'll take our next question from Kostas Biliouris with BMO Capital Markets. Your line is open.

Yeah, look, we're delighted with the progress of ATT program. [inaudible], it's advancing well, we've been able to demonstrate rapid and robust reductions in SAPPR data. It's going very well and we feel there's tremendous potential in the two indications that we are progressing for Alzheimer's disease and [inaudible] amyloid angiopathy. Pushkal, maybe talk a little bit about what we're looking at for the future. Absolutely. So taking your two questions and building on what Yvonne said, ATT is a very exciting program. We presented some data at AIC actually that showed that we had consistent knockdown in both [inaudible] alpha and beta but also the downstream disease related biomarkers [inaudible] 40 and 42 that are involved in CAA and Alzheimer's disease and continue to see very encouraging safety coming out of that program as well. So that program remains on track. We're very excited. As we've talked about, we recently kicked off the study in [inaudible] amyloid angiopathy, the second leading cause of hemorrhage. As you noted, we will be starting a study in Alzheimer's disease as well. We aren't ready to talk about the specifics of that. We're obviously working through our trial design but we'll share that with you shortly but we're very encouraged about this upstream mechanism. Its potential to be very differentiated in the disease space and hopefully have a favorable impact on the disease of Alzheimer's, which we all know adds a tremendous burden. With regard to your second question on [inaudible], look, I don't think there are any specific updates I want to give on the early pre-clinical programs other than to say what you heard in the main comments was just we are pushing very aggressively in terms of our 225 strategy to move a multitude of programs forward based on the excitement that we have around the platform here. And so we are on track for 3 plus INDs this year, 9 proprietary INDs by the end of '25 and a doubling of our pipeline by the end of next year. But we will give updates on those specific programs in due course and keep you posted. Next question.

Yvonne L. Greenstreet: Yeah, look, we're delighted with the progress of ATT program. [inaudible], it's advancing well, we've been able to demonstrate rapid and robust reductions in SAPPR data. It's going very well and we feel there's tremendous potential in the two indications that we are progressing for Alzheimer's disease and [inaudible] amyloid angiopathy. Pushkal, maybe talk a little bit about what we're looking at for the future.

Operator: Thank you. We'll take our next question from Costas Villarares with BMO Capital Markets. Your line is open.

Pushkal Garg: Absolutely. So taking your two questions and building on what Yvonne said, ATT is a very exciting program. We presented some data at AIC actually that showed that we had consistent knockdown in both [inaudible] alpha and beta but also the downstream disease related biomarkers [inaudible] 40 and 42 that are involved in CAA and Alzheimer's disease and continue to see very encouraging safety coming out of that program as well. So that program remains on track. We're very excited. As we've talked about, we recently kicked off the study in [inaudible] amyloid angiopathy, the second leading cause of hemorrhage. As you noted, we will be starting a study in Alzheimer's disease as well. We aren't ready to talk about the specifics of that. We're obviously working through our trial design but we'll share that with you shortly but we're very encouraged about this upstream mechanism. Its potential to be very differentiated in the disease space and hopefully have a favorable impact on the disease of Alzheimer's, which we all know adds a tremendous burden. With regard to your second question on [inaudible], look, I don't think there are any specific updates I want to give on the early pre-clinical programs other than to say what you heard in the main comments was just we are pushing very aggressively in terms of our 225 strategy to move a multitude of programs forward based on the excitement that we have around the platform here. And so we are on track for 3 plus INDs this year, 9 proprietary INDs by the end of '25 and a doubling of our pipeline by the end of next year. But we will give updates on those specific programs in due course and keep you posted.

Pushkal Garg: As we've talked about, we recently kicked off the study in [inaudible] amyloid angiopathy, the second leading cause of hemorrhage. As you noted, we will be starting a study in Alzheimer's disease as well. We aren't ready to talk about the specifics of that. We're obviously working through our trial design but we'll share that with you shortly but we're very encouraged about this upstream mechanism. Its potential to be very differentiated in the disease space and hopefully have a favorable impact on the disease of Alzheimer's, which we all know adds a tremendous burden. With regard to your second question on [inaudible], look, I don't think there are any specific updates I want to give on the early pre-clinical programs other than to say what you heard in the main comments was just we are pushing very aggressively in terms of our 225 strategy to move a multitude of programs forward based on the excitement that we have around the platform here. And so we are on track for 3 plus INDs this year, 9 proprietary INDs by the end of '25 and a doubling of our pipeline by the end of next year. But we will give updates on those specific programs in due course and keep you posted.

Pushkal Garg: With regard to your second question on [inaudible], look, I don't think there are any specific updates I want to give on the early pre-clinical programs other than to say what you heard in the main comments was just we are pushing very aggressively in terms of our 225 strategy to move a multitude of programs forward based on the excitement that we have around the platform here. And so we are on track for 3 plus INDs this year, 9 proprietary INDs by the end of '25 and a doubling of our pipeline by the end of next year. But we will give updates on those specific programs in due course and keep you posted.

Speaker Change: Thank you. We'll take our next question from Kostas Biliouris with BMO Capital Markets. Your line is open.

Yvonne L. Greenstreet: Next question.

Operator: Thank you. We'll take our next question from Kostas Biliouris with BMO Capital Markets. Your line is open.

Kostas Biliouris: Good morning everyone. Thanks for taking our question and congrats on the tremendous progress here. A quick question from us on real world data that was recently published on APPR Polyneuropathy. These studies showed that patients and their stabilizers progress very quickly, actually at a similar rate to national history, and then switch to ONPATTRO where the disease progression is almost halting. Any read through from this study to cardiomyopathy, and would you expect similar dynamics with AMVUTTRA here? Thank you. A great question. Pushkal, I think this is for you.

[Analyst] (BMO Capital Markets): Good morning, everyone. Thanks for taking our question and congrats on the tremendous progress here. A quick question from us on real-world data that recently was published on ATTR polyneuropathy. This study showed that patients under stabilizers progress very quickly, actually similar rate to natural history, and then switch to ONPATTRO where the disease progression is almost halting. Any read-through from this study to cardiomyopathy, and would you expect similar dynamics with AMVUTTRA here? Thank you.

Kostas Biliouris: Good morning, everyone. Thanks for taking our question and congrats on the tremendous progress here. A quick question from us on real-world data that recently was published on ATTR polyneuropathy. This study showed that patients under stabilizers progress very quickly, actually similar rate to natural history, and then switch to ONPATTRO where the disease progression is almost halting. Any read-through from this study to cardiomyopathy, and would you expect similar dynamics with AMVUTTRA here? Thank you.

Kostas Biliouris: Good morning everyone, thanks for taking our question and congrats on the tremendous progress we have made.

Yvonne L. Greenstreet: A great question. Pushkal, I think this is for you.

Pushkal Garg: Great question. Pushkal, I think this is for you.

Yvonne Greenstreet: Great question. Pushkal, I think this is for you.

Pushkal Garg: Yeah, thanks, Kostas. I think you were citing a paper that was recently published coming out of a European experience that looked at a cohort of patients who had been on [inaudible] and progressed, and a proportion of those patients then were put on ONPATTRO and actually seemed to have some stabilization in their disease. These were hereditary polyneuropathy patients.

[Analyst] (Jefferies LLC): Yeah, thanks, Costas. I think you were citing a paper that was recently published coming out of a European experience that looked at a cohort of patients who had been on tafamidis and progressed, and a proportion of those patients then were put on patisiran and actually seemed to have some stabilization in their disease. These were hereditary polyneuropathy patients. Look, I think it's very encouraging. We know that this is a complex disease. Patients do have a progressive progress with polyneuropathy and with cardiomyopathy. And so I don't think there's any question that there's an unmet need here for patients to have additional modes of therapy that can address what Tolga highlighted earlier is a very steadily progressive and fatal disease. And so I think we all agree.

Pushkal Garg: Yeah, thanks, Costas. I think you were citing a paper that was recently published coming out of a European experience that looked at a cohort of patients who had been on tafamidis and progressed, and a proportion of those patients then were put on patisiran and actually seemed to have some stabilization in their disease. These were hereditary polyneuropathy patients. Look, I think it's very encouraging. We know that this is a complex disease. Patients do have a progressive progress with polyneuropathy and with cardiomyopathy. And so I don't think there's any question that there's an unmet need here for patients to have additional modes of therapy that can address what Tolga highlighted earlier is a very steadily progressive and fatal disease. And so I think we all agree.

Speaker Change: who had been on tefamidus and progressed and a proportion of those patients then were put on Patro and actually seemed to have some stabilization of their disease. These were hereditary polyneuropathy patients.

Pushkal Garg: Look, I think it's very encouraging. We know that this is a complex disease. Patients do progress with polyneuropathy and with cardiomyopathy. And so I don't think there's any question that there's an unmet need here for patients to have additional modes of therapy that can address what Tolga highlighted earlier is a very steadily progressive and fatal disease. And so I think we all agree.

Kostas Biliouris: do progress with with polyneuropathy and with cardiomyopathy.

Christine Regan Lindenboom: And this is highlighted by the fact that, even when we had the Apollo data, Apollo B data, and we launched an EAP, there was tremendous need for patients who were on stabilizer therapy to get on to an additional orthogonal mechanism of action, and that study got enrolled very quickly. So we are very excited about the opportunity. Your patients need additional therapies, and we'll be bringing that forward we think now for the CM patients, as we have for the PN patients with AMVUTTRA.

[Analyst] (Jefferies LLC): This is highlighted by the fact that even when we had the HELIOS data, HELIOS-B data, and we launched an EAP, there was tremendous need for patients who were on stabilizer therapy to get onto an additional orthogonal mechanism of action. And that study enrolled very quickly. So we are very excited about the opportunity. Our patients need additional therapies, and we'll be bringing that forward, we think, now for the CM patients as we have for the PN patients with AMVUTTRA.

Pushkal Garg: This is highlighted by the fact that even when we had the HELIOS data, HELIOS-B data, and we launched an EAP, there was tremendous need for patients who were on stabilizer therapy to get onto an additional orthogonal mechanism of action. And that study enrolled very quickly. So we are very excited about the opportunity. Our patients need additional therapies, and we'll be bringing that forward, we think, now for the CM patients as we have for the PN patients with AMVUTTRA.

Speaker Change: and fatal disease. And so I think we all agree, and you know, this is highlighted by the fact that, you know, even when we had the Apollo data, Apollo B data, and we launched an EAP, there was tremendous need.

Kostas Biliouris: for patients who are on stabilizer therapy.

Pushkal Garg: Great. Next question.

Yvonne Greenstreet: Great. Next question.

Christine Regan Lindenboom: Great. Next question. Thank you. We'll take our next question from Jessica Fye with JP Morgan. Your line is open.

Yvonne L. Greenstreet: Great. Next question.

Operator: Thank you. We'll take our next question from Jessica Fry with J.P. Morgan. Your line is open.

Operator: Thank you. We'll take our next question from Jessica Fye with JP Morgan. Your line is open.

Speaker Change: Thank you. We'll take our next question from Jessica Fye with J.P. Morgan. Your line is open.

Jessica Fye: Hey, good morning. Thanks for taking my question. Can you set the stage for the level of detail we should expect with the interim results for Part B of the Phase I ALN ATT study later this year and how we should think about the communication or venue for that update? I'm also curious would you seek another partner for ALN ATT or do you now plan to keep that wholly owned? Thank you. I'll take the second question first. I mean, we're actually delighted to be progressing with ALN ATT.

[Analyst] (UBS Investment Bank): Great. Good morning. Thanks for taking my question. Can you set the stage around the level of detail we should expect with the interim results for Part B of the phase I ALN-APP study later this year and how we should think about the communication or kind of venue for that update? I'm also curious, would you seek another partner for ALN-APP, or do you now plan to keep that wholly owned? Thank you.

Jessica Fye: Great. Good morning. Thanks for taking my question. Can you set the stage around the level of detail we should expect with the interim results for Part B of the phase I ALN-APP study later this year and how we should think about the communication or kind of venue for that update? I'm also curious, would you seek another partner for ALN-APP, or do you now plan to keep that wholly owned? Thank you.

Jessica Fye: I'm also curious, would you seek another partner for ALAN APP or do you now plan to keep that wholly owned? Thank you.

Yvonne Greenstreet: Well, I'll take the second question first. I mean, we're actually delighted to be progressing ALN-APP. As I said, we're very excited about the two indications. We've already kicked off our phase II in patients with cerebral amyloid angiopathy, and planning to start the study in Alzheimer's disease at or around year-end. So we couldn't be more pleased to have another wholly owned program in our pipeline. And I look forward to moving these programs forward ourselves.

Yvonne L. Greenstreet: I'll take the second question first. I mean, we're actually delighted to be progressing with ALN ATT. As I said, we're very excited about the two indications. We've already kicked off our phase two in patients with cerebral amyloid angiopathy, and I'm planning to start the study in Alzheimer's disease at or around year end. So we couldn't be more pleased to have another wholly owned program in our pipeline. And I look forward to moving these programs forward ourselves.

Unknown Executive: As I said, we're very excited about the two indications. We've already kicked off our phase two in patients with cerebral amyloid angiopathy, and I'm planning to start the study in Alzheimer's disease at or around year end. So we couldn't be more pleased to have another wholly owned program in our pipeline. And I look forward to moving these programs forward ourselves. Yeah, just to comment on your question, it's a little early to tell you about the specific venue where we will be talking about the data, but I think what you'll see is starting to see some data with multiple doses in terms of again, the primary purpose of the study is on safety and pharmacodynamics and so what you'll be seeing is that with multiple dosing but overtime we'll be able to share more and more data coming out of that. But I think, again, our confidence in this program is highlighted by the fact that we've kicked off the study of phase two in CAA and we'll soon be kicking off a phase two in Alzheimer's disease, so we're very excited about the potential therapy and continue to investigate it. Huge potential, huge medical need there. We're very, very pleased to be moving it forward. Next question.

As I said, we're very excited about the two indications. We've already kicked off our phase two in patients with cerebral amyloid angiopathy, and I'm planning to start the study in Alzheimer's disease at or around year end. So we couldn't be more pleased to have another wholly owned program in our pipeline. And I look forward to moving these programs forward ourselves. Yeah, just to comment on your question, it's a little early to tell you about the specific venue where we will be talking about the data, but I think what you'll see is starting to see some data with multiple doses in terms of again, the primary purpose of the study is on safety and pharmacodynamics and so what you'll be seeing is that with multiple dosing but overtime we'll be able to share more and more data coming out of that. But I think, again, our confidence in this program is highlighted by the fact that we've kicked off the study of phase two in CAA and we'll soon be kicking off a phase two in Alzheimer's disease, so we're very excited about the potential therapy and continue to investigate it.

Speaker Change: As I said, we're very excited about, you know, the two indications really kicked off.

Speaker Change: We're in Phase 2 in patients with cerebral amyloid angiopathy and I'm planning to start the study in Alzheimer's disease at or around year end so we couldn't be more pleased to have another wholly owned program in our pipeline.

Pushkal Garg: Yeah, just to comment on your question, it's a little early to tell you about the specific venue where we will be talking about the data, but I think what you'll see is starting to see some data with multiple doses in terms of again, the primary purpose of the study is on safety and pharmacodynamics and so what you'll be seeing is that with multiple dosing but overtime we'll be able to share more and more data coming out of that. But I think, again, our confidence in this program is highlighted by the fact that we've kicked off the study of phase two in CAA and we'll soon be kicking off a phase two in Alzheimer's disease, so we're very excited about the potential therapy and continue to investigate it.

Pushkal Garg: Yeah. And any other comment? Yeah, just as a comment on your questions, it's a little early to tell you about the specific venue where we'll be talking about the data. But I think what you'll see is starting to see some data with multiple doses in terms of again, the primary purpose of the study is on safety and pharmacodynamics. And so what you'll be seeing is that with multiple dosing. But over time, we'll be able to share more and more data coming out of that. But I think, again, our confidence in this program is highlighted by the fact that we've kicked off a study of phase II in CAA, and we'll soon be kicking off a phase II in Alzheimer's disease. So we're very excited about the potential therapy and continue to investigate it.

Speaker Change: Yeah, just to comment on your question, it's a little early to tell you about the specific venue where we'll be talking about the data.

Jessica Fye: but you know I think what you'll see is starting to see some data with multiple doses in terms of

Yvonne Greenstreet: Huge potential, huge medical needs. We're very, very pleased to be moving it forward. Next question.

Yvonne L. Greenstreet: Huge potential, huge medical need there. We're very, very pleased to be moving it forward. Next question.

Operator: Thank you. We'll take our next question from David Lebowitz with Citi. Your line is open. Thank you very much for taking my question. I'm curious [inaudible] has been on the market for a couple quarters now. Has the nature of the discussion with physicians change since the drug launched at all and can you make any commentary on how the market is evolving relative to new competitive therapies? Great question. Tolga?

Operator: Thank you. We'll take our next question from David Lebowitz with Citi. Your line is open.

Operator: Thank you. We'll take our next question from David Liebowitz with Citi. Your line is open.

[Analyst] (Jefferies LLC): Thank you very much for taking my question. I'm curious. Certainly, since AMVUTTRA has been on the market for a couple of quarters now, have the nature of the discussions with physicians changed since the drug's launch at all? And can you make any commentary on how the market is evolving relative to a new competitive therapy?

David Lebowitz: Thank you very much for taking my question. I'm curious. Certainly, since AMVUTTRA has been on the market for a couple of quarters now, have the nature of the discussions with physicians changed since the drug's launch at all? And can you make any commentary on how the market is evolving relative to a new competitive therapy?

Speaker Change: Thank you. We'll take our next question from David Lebowitz with Citi. Your line is open.

David N. Lebowitz: Thank you very much for taking my question. I'm curious [inaudible] has been on the market for a couple quarters now. Has the nature of the discussion with physicians change since the drug launched at all and can you make any commentary on how the market is evolving relative to new competitive therapies?

Pushkal Garg: Great question. Tolga?

Yvonne Greenstreet: Great question. Tolga?

Operator: Great question. Tolga?

Tolga Tanguler: Yeah, I mean, as we've discussed before, this is a highly devastating disease, and there are still tens of thousands of patients that are expecting to get diagnosed and treated. Therefore, any addition to the market with increased promotional share of voice is a good thing. In respect to how the conversations are shaping up, as you can see from our Q2 results, now this is a two-player market in the U.S. where we continue to grow very rapidly, and I believe the nuances of the product will start becoming a lot clearer. As you know, the product profile of AMVUTTRA is one that rapidly knocks down the disease-causing protein durably and with a good, sustained quarterly injectable. That is becoming a good differentiator. And last but not least, how patients get on reimbursement and how they stay on reimbursement, and we're very pleased with the results that we've seen in Q2 and we expect to drive the momentum as such.

Yvonne Greenstreet: Yeah. I mean, as we discussed before, this is a highly devastating disease, and there are still tens of thousands of patients that are expecting to get diagnosed and treated. Therefore, any addition in the market with increased promotional share of voice is a good thing. In respect to how the conversations are shaping up, as you can see from our Q2 results, now this is a two-player market in the US where we continue to grow very rapidly. And I believe the nuances of the product start becoming a lot clearer. As you know, the product profile on AMVUTTRA is one that rapidly knocks down the disease-causing protein durably and with a good sustained quarterly injectable. That is becoming a good differentiator. And last but not least, of how patients get on the reimbursement and how they stay on the reimbursement.

Tolga Tanguler: Yeah. I mean, as we discussed before, this is a highly devastating disease, and there are still tens of thousands of patients that are expecting to get diagnosed and treated. Therefore, any addition in the market with increased promotional share of voice is a good thing. In respect to how the conversations are shaping up, as you can see from our Q2 results, now this is a two-player market in the US where we continue to grow very rapidly. And I believe the nuances of the product start becoming a lot clearer. As you know, the product profile on AMVUTTRA is one that rapidly knocks down the disease-causing protein durably and with a good sustained quarterly injectable. That is becoming a good differentiator. And last but not least, of how patients get on the reimbursement and how they stay on the reimbursement.

Speaker Change: Yeah, I mean, as we discussed before, this is a highly devastating disease, and there's still tens of thousands of patients that are expecting to get diagnosed and treated. Therefore, any addition,

Speaker Change: in the markets with, you know, increased promotional share of voice is a good thing.

Speaker Change: Now this is a two-player market in the U.S. where we continue to grow very rapidly and I believe the nuances of the products start becoming a lot clearer.

Speaker Change: As you know, the product profile on Wootra...

Speaker Change: is one that rapidly knocks down the disease-causing protein.

Speaker Change: Endurably and with a good sustained quarterly injectables.

Tolga Tanguler: And last but not least, how patients get on reimbursement and how they stay on reimbursement, and we're very pleased with the results that we've seen in Q2 and we expect to drive the momentum as such. Thank you. We'll take our next question from Gena Wang with Barclays. Your line is open.

And last but not least, how patients get on reimbursement and how they stay on reimbursement, and we're very pleased with the results that we've seen in Q2 and we expect to drive the momentum as such.

Speaker Change: That is becoming a good differentiator and last but not least of how patients get on the reimbursement and how they stay on the reimbursement and we're very pleased with the results that we've seen in Q2 and we expect to drive the momentum as such.

Yvonne Greenstreet: We're very pleased with the results that we've seen in Q2. We expect to drive the momentum as such.

Tolga Tanguler: We're very pleased with the results that we've seen in Q2. We expect to drive the momentum as such.

Pushkal Garg: Excellent. Thank you. Thanks for taking my question.

David Lebowitz: Excellent. Thank you. Thanks for taking my question.

Operator: Thank you. We'll take our next question from Gena Wang with Barclays. Your line is open.

Operator: Thank you. We'll take our next question from Gina Wang with Barclays. Your line is open.

Speaker Change: Thank you for taking my question.

Pushkal Garg: Thank you. I will also ask another question regarding AMVUTTRA. Given this is Part B coverage, have you seen any pattern in terms of the patient population regarding sorry, the pattern from ATTR polyneuropathy patient regarding patient population and the geographic locations? And quickly on the ALN-TTRsc04, any latest thoughts on phase III trial design?

Gena Wang: Thank you. I will also ask another question regarding AMVUTTRA. Given this is Part B coverage, have you seen any pattern in terms of the patient population regarding sorry, the pattern from ATTR polyneuropathy patient regarding patient population and the geographic locations? And quickly on the ALN-TTRsc04, any latest thoughts on phase III trial design?

Gena Wang: Thank you. I will also ask another question regarding AMVUTTRA. Given this Part B coverage, have you seen any pattern in terms of the patient population regarding, sorry, the pattern from ATTR polyneuropathy patients regarding patient population and geographic locations? And quickly on the TTR SC04, any latest thoughts on Phase 3 trial design? Yeah, maybe I'll start with the TTR SCO4 question. I mean, clearly, this is an opportunity to build a durable franchise in TTR for Alnylam. We've seen rapid knockdown, very durable knockdown and we're looking at a program that potentially has improved knockdowns with six months to annual dosing, so we're really, really excited about moving forward on TTR SCO4. Still early to comment on the specifics of the clinical program at this point in time but there will be more to come as we get to the end of this year. Tolga, do you want to take the question on reimbursements? Yeah, so I think one thing to really keep in mind is we strictly adhere to the patient [inaudible] that Alnylam has established over the years. And through that, what we will look at is the [inaudible]. Given that our product is reimbursed because it's a physician-administered product through Part B, what we've seen is nearly 70% of our patients remain, have zero co-pay, and up to 80% of patients pay less than $2,000.

Speaker Change: Given this a Part B coverage, have you seen any pattern in terms of

Speaker Change: Unknown Speaker You know the patient population regarding sorry the prior you know the pattern from ATTR neuropathy patient regarding patient population in a geography location.

Yvonne Greenstreet: Yeah, maybe I'll start with the TTRsc04 question. I mean, clearly, this is an opportunity to really build a durable franchise in TTR for Alnylam, and we've seen rapid knockdown, very durable knockdown. And we're looking at a program that potentially has improved knockdown with six-monthly or annual dosing. So we're really, really excited about moving forward TTRsc04. It's a little early to comment on the specifics of the clinical program at this point in time, but there will be more to come as we get to the end of this year. Tolga, do you want to take the question on?

Speaker Change: Yeah, maybe I'll start with the CTR-SO4 question. I mean, clearly, this is a, you know, an opportunity to really build a durable franchise.

Speaker Change: program that potentially has, you know, improved a knockdown with, you know, six-monthly or annual dosing. So we're really, really excited about that.

Tolga Tanguler: Yeah, so I think one thing to really keep in mind is we strictly adhere to the patient [inaudible] that Alnylam has established over the years. And through that, what we will look at is the [inaudible]. Given that our product is reimbursed because it's a physician-administered product through Part B, what we've seen is nearly 70% of our patients remain, have zero co-pay, and up to 80% of patients pay less than $2,000.

Christine Lindenboom: Reimbursement?

Tolga Tanguler: Reimbursement?

Yvonne Greenstreet: On reimbursement, yeah.

Christine Lindenboom: Yeah. So I mean, I think one thing is really to keep in mind is we strictly adhere to the patient access philosophy that Alnylam has established over the years. And through that, what we really look at is the copay burden on the patients. Given that our product is reimbursed because it's a physician-administered product through Part B, what we've seen is nearly 70% of our patients have zero copay, and up to 80% of patients pay less than $2,000. This really puts us in an important position where the copay burden is either less or similar to those products that would be reimbursed in Part D with the new IRA redesign. So we believe this is a good mix of reimbursement.

Tolga Tanguler: Yeah. So I mean, I think one thing is really to keep in mind is we strictly adhere to the patient access philosophy that Alnylam has established over the years. And through that, what we really look at is the copay burden on the patients. Given that our product is reimbursed because it's a physician-administered product through Part B, what we've seen is nearly 70% of our patients have zero copay, and up to 80% of patients pay less than $2,000. This really puts us in an important position where the copay burden is either less or similar to those products that would be reimbursed in Part D with the new IRA redesign. So we believe this is a good mix of reimbursement.

Speaker Change: Given that our product is reimbursed because it's a physician-administered product through Part B,

Tolga Tanguler: This really puts us in an important position where the co-pay burden is either less or similar to those products that would be reimbursed in Part D with the new IRA redesign. So we believe this is a good mix of reimbursement. And when it comes to global, we've been able to compete in a very price-sensitive markets across Europe and Japan in polyneuropathy in a very competitive way where we are driving about over 90% market share versus the stabilizer product that's in the market. Therefore, we really like where we are in terms of our reimbursement policy, and obviously, we're keeping an eye on it to make sure that patients get on this treatment if their physicians decide to do so.

Christine Lindenboom: And when it comes to global, we've been able to compete in very price-sensitive markets across Europe and Japan in polyneuropathy in a very competitive way where we are driving about over 90% market share versus the stabilizer product that's in the market. Therefore, we really like where we are in terms of our reimbursement policy. And obviously, we're keeping an eye on it to make sure that patients get on this treatment if their physicians decide to do so.

Tolga Tanguler: And when it comes to global, we've been able to compete in very price-sensitive markets across Europe and Japan in polyneuropathy in a very competitive way where we are driving about over 90% market share versus the stabilizer product that's in the market. Therefore, we really like where we are in terms of our reimbursement policy. And obviously, we're keeping an eye on it to make sure that patients get on this treatment if their physicians decide to do so.

Speaker Change: in a polyneuropathy, in a very...

Christine Regan Lindenboom: Therefore, we really like where we are in terms of our reimbursement policy, and obviously, we're keeping an eye on it to make sure that patients get on this treatment if their physicians decide to do so. Next question.

Therefore, we really like where we are in terms of our reimbursement policy, and obviously, we're keeping an eye on it to make sure that patients get on this treatment if their physicians decide to do so.

Pushkal Garg: Thank you.

Gena Wang: Thank you.

Yvonne L. Greenstreet: Next question.

Operator: Thank you. We'll take our next question from Ritu Bharel with TD Cowen. Your line is open. Hi guys, thanks for taking the question. I wanted to ask Tolga just how you are now sort of positioning and it sounds like you've been positioning for a while AMVUTTRA affecting TTR CM as far as actual commercial strategies. Jeff mentioned a scalable salesforce; can you talk about the magnitude of that and are you changing the mix of targeting of the salesforce. And then in our doc calls, they've mentioned that they do expect despite the wealth of data that this is going to be a commercial insensitive market. How are things like label language, KPCQ, New York Heart Association, those are real endpoints in your study, how are they going to factor into your marketing message? How important are they or is it going to be mortality driven all the way? Thanks. Tolga, straight to you. It's a terrific question.

Pushkal Garg: Great question.

Yvonne Greenstreet: Great question.

Operator: Thank you. We'll take our next question from Ritu Berel with TD Cowen. Your line is open.

Speaker Change: Thank you.

Pushkal Garg: Hi, guys. Thanks for taking the question. I wanted to ask Tolga just how you are now sort of positioning, and it sounds like you've been positioning for a while AMVUTTRA in TTR-CM. As far as actual commercial strategies, Jeff mentioned a scale-up of the sales force. Can you talk about the magnitude of that, and are you changing the mix of targeting of the sales force? And then in our doc calls, our doc calls have mentioned that they do expect, despite the wealth of data, that this is going to be a commercially sensitive market. How are things like label language, KCCQ, New York Heart Association, those are real endpoints in your study. How are they going to factor into your marketing message? How important are they, or is it going to be mortality-driven all the way? Thanks.

Ritu Baral: Hi, guys. Thanks for taking the question. I wanted to ask Tolga just how you are now sort of positioning, and it sounds like you've been positioning for a while AMVUTTRA in TTR-CM. As far as actual commercial strategies, Jeff mentioned a scale-up of the sales force. Can you talk about the magnitude of that, and are you changing the mix of targeting of the sales force? And then in our doc calls, our doc calls have mentioned that they do expect, despite the wealth of data, that this is going to be a commercially sensitive market. How are things like label language, KCCQ, New York Heart Association, those are real endpoints in your study. How are they going to factor into your marketing message? How important are they, or is it going to be mortality-driven all the way? Thanks.

Speaker Change: Hi guys, thanks for taking the question. I wanted to ask to Tolga just how you are now sort of

Speaker Change: Jeff mentioned a scale up of the sales force. Can you talk about the magnitude of that? And are you changing the mix of targeting of the sales force? And then in our doc calls, our doc calls have mentioned that

Speaker Change: They do expect, despite the wealth of data, that this is going to be a commercially sensitive market.

Speaker Change: KCCQ, New York Heart Association. Those are real endpoints in your study. How are they going to factor into your marketing message? How important are they? Or is it going to be mortality driven all the way? Thanks.

Yvonne L. Greenstreet: Tolga, straight to you. It's a terrific question.

Tolga Tanguler: Sure. I mean, one thing, I just want to make clear, obviously, we're going to start off with a very strong foundation where this disease is being treated by multidisciplinary centers and where our organization is there. But when it comes to positioning, I want to make it very clear that we are strictly promoting our polyneuropathy indication and we will adhere to that until, obviously, we receive the label expansion. So I just want to make that clear.

Yvonne Greenstreet: Tolga, straight to you. That's a terrific question. Sure. I mean, one thing I just want to make it clear, obviously, we're going to start off with a very strong foundation where this disease is being treated by multidisciplinary centers and where our organization is there. But when it comes to positioning, I want to make it very clear that we are strictly promoting our polyneuropathy indication, and we will adhere to that until, obviously, we receive the label expansion. So I just want to make that clear. Now, again, I think, as you highlighted, one of our great advantages is we have deep experience with TTR centers. We've been able to expand our polyneuropathy prescriber base by 50%. We have a well-integrated customer team. Now, we highlight the fact that the prevalence of this disease obviously tenfolds. Having said that, the number of prescribers is not tenfold.

Yvonne Greenstreet: Tolga, straight to you. That's a terrific question.

Tolga Tanguler: Sure. I mean, one thing I just want to make it clear, obviously, we're going to start off with a very strong foundation where this disease is being treated by multidisciplinary centers and where our organization is there. But when it comes to positioning, I want to make it very clear that we are strictly promoting our polyneuropathy indication, and we will adhere to that until, obviously, we receive the label expansion. So I just want to make that clear. Now, again, I think, as you highlighted, one of our great advantages is we have deep experience with TTR centers. We've been able to expand our polyneuropathy prescriber base by 50%. We have a well-integrated customer team. Now, we highlight the fact that the prevalence of this disease obviously tenfolds. Having said that, the number of prescribers is not tenfold.

Speaker Change: where this disease is being treated by multidisciplinary centers and where we're our organization is there. But when it comes to positioning, I want to make it very clear that

Tolga Tanguler: Now, again, I think, as you highlighted, one of our great advantages is that we have deep experience with TTR centers. We've been able to expand our polyneuropathy prescriber base by 50%. We have a well-integrated customer team. Now, we highlight the fact that the prevalence of this disease is obviously tenfold. Having said that, the number of prescribers is not tenfold. It's a smaller magnitude of the prescriber base. Therefore, we believe we can actually scale this up in the appropriate way. And then when it comes to rare diseases, having an integrated customer-facing team where you have good coverage of reimbursement support, and you have good coverage of medical and field organization support is going to be key. We have that.

Tolga Tanguler: Now, we highlight the fact that the prevalence of this disease is obviously tenfold. Having said that, the number of prescribers is not tenfold. It's a smaller magnitude of the prescriber base.

Speaker Change: We have a well-integrated customer team. Now, we highlight the fact that, you know, the prevalence of this disease obviously tenfold.

Yvonne Greenstreet: It's a lesser magnitude of prescriber base. Therefore, we believe we can actually scale this up in the appropriate way. And then when it comes to, in rare diseases, having an integrated customer-facing team where you have good coverage of reimbursement support, you have good coverage of medical, and field organization support is going to be key. We have that. And the last piece, I think, of the puzzle is a very good, strong established patient support services where we are actually quite pleased with the time to treatment from patient start forms into patients getting reimbursed and starting on therapy. Now, those are obviously some of the capabilities where we're keeping an eye on, and we're going to scale that up.

Tolga Tanguler: It's a lesser magnitude of prescriber base. Therefore, we believe we can actually scale this up in the appropriate way. And then when it comes to, in rare diseases, having an integrated customer-facing team where you have good coverage of reimbursement support, you have good coverage of medical, and field organization support is going to be key. We have that. And the last piece, I think, of the puzzle is a very good, strong established patient support services where we are actually quite pleased with the time to treatment from patient start forms into patients getting reimbursed and starting on therapy. Now, those are obviously some of the capabilities where we're keeping an eye on, and we're going to scale that up.

Speaker Change: Having said that, the number of prescribers is not tenfold. It's a lesser magnitude of prescriber base. Therefore, we believe we can actually scale this up in the appropriate way. And then when it comes to, you know, in rare diseases,

Tolga Tanguler: Therefore, we believe we can actually scale this up in the appropriate way. And then when it comes to rare diseases, having an integrated customer-facing team where you have good coverage of reimbursement support, and you have good coverage of medical and field organization support is going to be key. We have that.

Speaker Change: having an integrated customer facing team.

Speaker Change: where you have good coverage of reimbursement support, you have good coverage of medical and field organization support is going to be key. We have that.

Tolga Tanguler: And the last piece, I think, of the puzzle is a very good, strong, established patient support services where we are actually quite pleased with the time to treatment from patient start forms into patients getting reimbursed and starting therapy. Now, those are obviously some of the capabilities that we're keeping an eye on, and we're going to scale that up. Now, when it comes to the second part of your question, in terms of labeling and how we're going to be positioning the product, obviously that's going to be dependent on the FDA and we don't comment given the label discussions that we have. I think what you will see at ESC is going to give you a further color about the robustness of this data and how we can actually be able to communicate effectively both primary composite and secondary end point as well as the low cause mortality. We believe there's going to be a clear differentiation for our product. And last but not least is that the product profile itself. Given that this is a quickly progressing irreversible disease, to be able to demonstrate a rapid knockdown of a disease causing pathogen as quickly as possible is going to be important. Given that how patients actually quickly get on access to this treatment is going to be very critical. So combining all that with the data that we have with Helios B and the product profile, we really do strongly believe physicians will choose AMVUTTRA if approved as a first line product given where the disease is, given what the product is and given when we have the data. Thanks, Tolga. Next question.

And the last piece, I think, of the puzzle is a very good, strong, established patient support services where we are actually quite pleased with the time to treatment from patient start forms into patients getting reimbursed and starting therapy. Now, those are obviously some of the capabilities that we're keeping an eye on, and we're going to scale that up. Now, when it comes to the second part of your question, in terms of labeling and how we're going to be positioning the product, obviously that's going to be dependent on the FDA and we don't comment given the label discussions that we have. I think what you will see at ESC is going to give you a further color about the robustness of this data and how we can actually be able to communicate effectively both primary composite and secondary end point as well as the low cause mortality. We believe there's going to be a clear differentiation for our product. And last but not least is that the product profile itself. Given that this is a quickly progressing irreversible disease, to be able to demonstrate a rapid knockdown of a disease causing pathogen as quickly as possible is going to be important. Given that how patients actually quickly get on access to this treatment is going to be very critical. So combining all that with the data that we have with Helios B and the product profile, we really do strongly believe physicians will choose AMVUTTRA if approved as a first line product given where the disease is, given what the product is and given when we have the data.

Speaker Change: And the last piece, I think, of the puzzle is a very good, strong, established patient support services.

Yvonne Greenstreet: Now, when it comes to your second part of your question, in terms of labeling, how we're going to be positioning the product, obviously, that's going to be depending on the FDA, and we don't comment given the label discussions that we have. I think what you will see at ESC is going to give you a further color about the robustness of this data and how we can actually be able to communicate effectively both primary, composite, and secondary endpoints, as well as the all-cause mortality. We believe there's going to be a clear differentiation for our product. And last but not least is the product profile itself. I mean, given that this is a swiftly progressing, irreversible disease, to be able to demonstrate a rapid knockdown that really knocks down the disease-causing pathogen as quickly as possible is going to be important.

Tolga Tanguler: Now, when it comes to your second part of your question, in terms of labeling, how we're going to be positioning the product, obviously, that's going to be depending on the FDA, and we don't comment given the label discussions that we have. I think what you will see at ESC is going to give you a further color about the robustness of this data and how we can actually be able to communicate effectively both primary, composite, and secondary endpoints, as well as the all-cause mortality. We believe there's going to be a clear differentiation for our product. And last but not least is the product profile itself. I mean, given that this is a swiftly progressing, irreversible disease, to be able to demonstrate a rapid knockdown that really knocks down the disease-causing pathogen as quickly as possible is going to be important.

Speaker Change: where we're keeping an eye on and we're going to scale that up. Now when it comes to your second part of your question in terms of labeling how we're going to be positioning the product

Now, when it comes to the second part of your question, in terms of labeling and how we're going to be positioning the product, obviously that's going to be dependent on the FDA and we don't comment given the label discussions that we have. I think what you will see at ESC is going to give you a further color about the robustness of this data and how we can actually be able to communicate effectively both primary composite and secondary end point as well as the low cause mortality. We believe there's going to be a clear differentiation for our product. And last but not least is that the product profile itself. Given that this is a quickly progressing irreversible disease, to be able to demonstrate a rapid knockdown of a disease causing pathogen as quickly as possible is going to be important. Given that how patients actually quickly get on access to this treatment is going to be very critical. So combining all that with the data that we have with Helios B and the product profile, we really do strongly believe physicians will choose AMVUTTRA if approved as a first line product given where the disease is, given what the product is and given when we have the data.

Speaker Change: Obviously, that's going to be depending on the FDA and where we don't comment, given the, you know, the label discussions that we have. I think what you will see at ESC is going to give you a further color about

Speaker Change: The robustness of this data and how we can actually be able to communicate effectively both primary, composite, and secondary endpoints, as well as the all-cause mortality. We believe there's going to be a clear differentiation for our product. And last but not least is the product profile itself.

Speaker Change: I mean, given that this is a swiftly progressing, irreversible disease, to be able to demonstrate a rapid knockdown that really knocks down the disease-causing pathogen as quickly as possible is going to be important.

Yvonne Greenstreet: Given the convenience of quarterly dosing is going to be important. Given that, how patients actually quickly get on access to this treatment is going to be very critical. So combining all this with the data that we have with HELIOS-B and the product profile, we really do strongly believe physicians will choose AMVUTTRA if approved as a first-line product, given where the disease is, given what the product is, and given where we have the data.

Tolga Tanguler: Given the convenience of quarterly dosing is going to be important. Given that, how patients actually quickly get on access to this treatment is going to be very critical. So combining all this with the data that we have with HELIOS-B and the product profile, we really do strongly believe physicians will choose AMVUTTRA if approved as a first-line product, given where the disease is, given what the product is, and given where we have the data.

Speaker Change: to this treatment is going to be very critical so combining all this with the data that we have with Helios P and the product profile we really do strongly believe physicians will choose Almutra if approved

Speaker Change: as a first-line product, given where the disease is, given what the product is, and given where we have the data.

Pushkal Garg: Thanks, Tolga. Next question.

Yvonne Greenstreet: Thanks, Tolga. Next question.

Yvonne L. Greenstreet: Thanks, Tolga. Next question.

Operator: Thank you. We'll take our next question from Salveen Richter with Goldman Sachs. Your line is open.

Operator: Thank you. I'll take our next question from Salveen Richter with Goldman Sachs. Your line is open.

Tolga: Thanks, Tolga.

Speaker Change: Next question. Thank you. I'll take our next question from Salveen Richter with Goldman Sachs. Your line is open.

Unknown: Hi, thanks for taking my question and congrats on the results. This is Tommie on for Salveen. Just a question about your discussions with KOLs and cardiologists. Have you heard a number or range for the additive benefit on top of TAFs that would be considered meaningful in Helios B? And just to follow up on the commercial questions, over the longer term, what's your strategy here for growing the market beyond taking care of or adding on top of [inaudible]? Thank you. Yeah, so maybe I can take the first part of your question in terms of is there some numerical target in terms of benefit on top of [inaudible].

[Analyst] (BMO Capital Markets): Hi. Thanks for taking my question, and congrats on the results. This is Tommy Ohm for Salveen. Just a question on your discussions with KOLs and cardiologists. Have you heard a number or range for the additive benefit on top of tafamidis that would be considered meaningful in HELIOS-B? And just to follow up on the commercial questions, over the longer term, what's your strategy here for growing the market beyond taking share or adding on top of tafamidis? Thank you so much.

Salveen Richter: Hi. Thanks for taking my question, and congrats on the results. This is Tommy Ohm for Salveen. Just a question on your discussions with KOLs and cardiologists. Have you heard a number or range for the additive benefit on top of tafamidis that would be considered meaningful in HELIOS-B? And just to follow up on the commercial questions, over the longer term, what's your strategy here for growing the market beyond taking share or adding on top of tafamidis? Thank you so much.

Tommie: Hi, thanks for taking my question and congrats on the results. This is Tommie on for Salveen. Just a question on your discussions with KOLs and cardiologists. Have you heard a number or range for the additive benefit on top of TAFs that would be considered meaningful in heliocytes? And just to follow up on the commercial questions, over the longer term, what's your strategy here for growing the market beyond taking care or adding on top of to salmonists? Thank you so much.

Jeffrey Poulton: Yeah, so maybe I can take the first part of your question in terms of is there some numerical target in terms of benefit on top of [inaudible]. I think really what I would say is the feedback that we've gotten all along, and I think it has only been accentuated since we've shared the top line results with KOLs is just the enthusiasm for a new medicine to help these patients first and foremost. Second of all, what they're seeing from the top line results is an opportunity for this drug to actually access the broad spectrum of patients with this disease.

Unknown Executive: Just a question about your discussions with KOLs and cardiologists. Have you heard a number or range for the additive benefit on top of TAFs that would be considered meaningful in helioski? And just to follow up on the commercial questions, over the longer term, what's your strategy here for growing the market beyond taking care of or adding on top of salmonists? Thank you. Yeah, so maybe I can take the first part of your question in terms of is there some numerical target in terms of benefit on top of defaminants?

Pushkal Garg: Yeah. So maybe I can take the first part of your question in terms of, is there some numerical target in terms of benefit on top of tafamidis. I think really what I would say is the feedback that we've gotten all along, and I think has only been accentuated since we've shared the top-line results with KOLs, is just the enthusiasm for a new medicine to help these patients, first and foremost. Second of all, what they're seeing from the top-line results is an opportunity for this drug to actually access the broad spectrum of patients with this disease. We saw strong efficacy as a monotherapy across all the endpoints.

Speaker Change: Yeah, so maybe I can take the first part of your question in terms of, is there some numerical target in terms of...

Unknown Executive: I think really what I would say is the feedback that we've gotten all along, and I think it has only been accentuated since we've shared the top line results with KOLs is just the enthusiasm for a new medicine to help these patients first and foremost. Second of all, what they're seeing from the top line results is an opportunity for this drug to actually access the broad spectrum of patients with this disease.

Speaker Change: benefit on top of the famine is I think really what I would say is

Unknown Executive: We saw strong efficacy as monotherapy across all the endpoints, but we saw equally strong efficacy in the overall population, which I'll remind you includes 40% of patients who start on background TAP and a good proportion of people who actually added on TAP and added on STLT2 inhibitors, had diuretic intensification.

Pushkal Garg: But we saw equally strong efficacy in the overall population, which, I'll remind you, includes 40% of patients who start on background TAF and a good proportion of people who actually added on TAF, added on SGLT2 inhibitors, had diuretic intensification. And so, and I think as some have noticed from the top-line results, there is, if you just look at the mortality numbers, the strength of the data in the overall population, both in terms of the actual magnitude of effect as well as the p-value, were somewhat stronger, which implies a pretty substantial effect in the add-on population. Now, that's encouraging because it wasn't powered or designed to show an effect in that population, but to see what we're seeing is consistent evidence of additive efficacy, I think, is encouraging.

Speaker Change: We saw equally strong efficacy in the overall population, which, I'll remind you, includes

Speaker Change: and a good proportion of people who actually added on TAP and added on SGLT2 inhibitors.

Unknown Executive: And I think as some have noticed from the top line results, if you just look at the mortality numbers, the strength of the data in the overall population, both in terms of the actual magnitude of effect as well as the P value, is somewhat stronger, which implies a pretty substantial effect in the add-on population. Now, that's encouraging because it wasn't powered or designed to show an effect in that population, but to see what we're seeing is consistent evidence of additive efficacy, I think is encouraging. So, there's no numerical target, but I think what people are seeing is a picture of a drug that's emerging for them that looks quite, to be quite effective for this disease.

Speaker Change: had diuretic intensification.

Speaker Change: And so, you know, and I think as some have noticed from the top-line results...

Speaker Change: Now, that's encouraging because it wasn't powered or designed to show an effect in that population. But to see what we're seeing is consistent evidence of additive efficacy, I think is encouraging. So there's no numerical target. But I think what people are seeing is a picture of a drug that's emerging to them that looks

Unknown Executive: So, there's no numerical target, but I think what people are seeing is a picture of a drug that's emerging for them that looks quite, to be quite effective for this disease. I think Tolga a few words about the market. We've talked about how we think about the market pre-tax loss of exclusivity and post-tax loss of [inaudible], we thought you could make a few comments on. Yeah, I mean, we believe that given this is a rare disease this is unusual for a combination therapy to be used given some of the access challenges. However, I think we believe given the data set we believe there is going to be some combination used earlier on prior to the task exclusivity. But to your point, what's really important is the category growth. What we've seen is given that diagnostic tools have advanced over the last six years, there's easy access for patients to get diagnosed early. I think having increased share of voice and promotional awareness of this category is going to help. The only available treatment has done a phenomenal job of expanding the diagnosis rate and with that, voices in this category are only going to accelerate the diagnosis and treatment rate and we believe those patients deserve many options to be treated. Jeff, anything you want to add?

So, there's no numerical target, but I think what people are seeing is a picture of a drug that's emerging for them that looks quite, to be quite effective for this disease. I think Tolga a few words about the market. We've talked about how we think about the market pre-tax loss of exclusivity and post-tax loss of [inaudible], we thought you could make a few comments on.

So, there's no numerical target, but I think what people are seeing is a picture of a drug that's emerging for them that looks quite, to be quite effective for this disease.

Pushkal Garg: So there's no numerical target, but I think what people are seeing is a picture of a drug that's emerging to them that looks quite effective for this disease. I think, Tolga, a few words about the market. We've talked about how we think about the market pre-TAF loss of exclusivity, and post-TAF loss of exclusivity, perhaps you could make a few comments on thinking there.

Pushkal Garg: So there's no numerical target, but I think what people are seeing is a picture of a drug that's emerging to them that looks quite effective for this disease.

Yvonne Greenstreet: I think, Tolga, a few words about the market. We've talked about how we think about the market pre-TAF loss of exclusivity, and post-TAF loss of exclusivity, perhaps you could make a few comments on thinking there.

Yvonne L. Greenstreet: I think Tolga a few words about the market. We've talked about how we think about the market pre-tax loss of exclusivity and post-tax loss of [inaudible], we thought you could make a few comments on.

Christine Lindenboom: Yeah. I mean, we believe given that this is a rare disease, it's unusual for a combination therapy to be used given some of the access challenges. However, I think we believe, given the data set, we believe there's going to be some combination use early on prior to the TAF exclusivity. But to your point, what's really important is the category growth. What we've seen is given that the diagnostic tools have advanced over the last six years, there's easy access for patients to get diagnosed early. I think having an increased share of voice and promotional awareness of this category is going to help. The only available treatment has actually done a phenomenal job of expanding the diagnosis rates. And with added voices in this category, it's only going to accelerate the diagnosis and treatment rates. And we believe those patients deserve many options to be treated.

Tolga Tanguler: Yeah. I mean, we believe given that this is a rare disease, it's unusual for a combination therapy to be used given some of the access challenges. However, I think we believe, given the data set, we believe there's going to be some combination use early on prior to the TAF exclusivity. But to your point, what's really important is the category growth. What we've seen is given that the diagnostic tools have advanced over the last six years, there's easy access for patients to get diagnosed early. I think having an increased share of voice and promotional awareness of this category is going to help. The only available treatment has actually done a phenomenal job of expanding the diagnosis rates. And with added voices in this category, it's only going to accelerate the diagnosis and treatment rates. And we believe those patients deserve many options to be treated.

Tolga Tanguler: Yeah, I mean, we believe that given this is a rare disease this is unusual for a combination therapy to be used given some of the access challenges. However, I think we believe given the data set we believe there is going to be some combination used earlier on prior to the task exclusivity. But to your point, what's really important is the category growth. What we've seen is given that diagnostic tools have advanced over the last six years, there's easy access for patients to get diagnosed early. I think having increased share of voice and promotional awareness of this category is going to help. The only available treatment has done a phenomenal job of expanding the diagnosis rate and with that, voices in this category are only going to accelerate the diagnosis and treatment rate and we believe those patients deserve many options to be treated. Jeff, anything you want to add?

Speaker Change: What's really important is the category growth. What we've seen is...

Speaker Change: Given that the diagnostic tools have advanced over the last six years, there's easy access for patients to get diagnosed early.

Pushkal Garg: Jeff, anything you want to add?

Yvonne Greenstreet: Jeff, anything you want to add?

Yvonne L. Greenstreet: Jeff, anything you want to add?

Unknown Executive: I don't have anything further to add, no. Great. Thank you. Thank you, Tolga.

Jeffrey Poulton: I don't have anything further to add, no.

Christine Lindenboom: I don't have anything further to add. No.

Jeff Poulton: I don't have anything further to add. No.

Pushkal Garg: Great. Thank you. Thank you. Thanks, Tolga.

Yvonne Greenstreet: Great. Thank you. Thank you. Thanks, Tolga.

Speaker Change: Jeff, anything you want to add? I don't have anything further to add, no. Great, thank you. Thank you. Thank you so much.

Yvonne L. Greenstreet: Great. Thank you. Thank you, Tolga.

Operator: Thank you. We'll take our next question from Mike Ulz with Morgan Stanley. Your line is open. Good morning. Thanks for taking the question and congrats on the quarter as well. Maybe just a quick follow up on some prior questions as well in terms of the market opportunity for TTR CM. Can you just talk a little bit about about why 80% of patients go untreated currently? It sounds like diagnosis is probably one of the key factors but what are some of the other factors and then how do you reduce that going forward? Thanks.

Operator: Thank you. We'll take our next question from Mike Ulz with Morgan Stanley. Your line is open.

Operator: Thank you. We'll take our next question from Mike Oultz with Morgan Stanley. Your line is open.

Mike Ulz: Good morning. Thanks for taking the question and congrats on the quarter as well. Maybe just a quick follow up on some prior questions as well in terms of the market opportunity for TTR CM. Can you just talk a little bit about about why 80% of patients go untreated currently? It sounds like diagnosis is probably one of the key factors but what are some of the other factors and then how do you reduce that going forward? Thanks.

[Analyst] (Jefferies LLC): Good morning. Thanks for taking the question, and congrats on the quarter as well. Maybe just a quick follow-up on some prior questions in terms of the market opportunity for TTR-CM. Can you just talk a little bit about why 80% of patients go untreated currently? It sounds like diagnosis is probably one of the key factors, but what are some of the other factors, and then how do you reduce that going forward? Thanks.

Mike Ulz: Good morning. Thanks for taking the question, and congrats on the quarter as well. Maybe just a quick follow-up on some prior questions in terms of the market opportunity for TTR-CM. Can you just talk a little bit about why 80% of patients go untreated currently? It sounds like diagnosis is probably one of the key factors, but what are some of the other factors, and then how do you reduce that going forward? Thanks.

Tolga Tanguler: Tolga, I think another one for you. Yeah, look, this is a disease, especially in the wild type cardiomyopathy patients don't start having these symptoms until sometimes it's too late, so that's one of the key drivers. The second thing is, there are only a few multidisciplinary centers. What we've seen is those multidisciplinary centers start expanding more and the awareness of how the disease actually manifests itself is being picked up by authority. As much as we say [inaudible] polyneuropathy, it's still a rare disease. The U.S has less than 200,000 patients. Therefore, it is not as common as what doctors used to see, cardiologists or neurologist or even in some cases, orthopedic surgeons where they see bilateral carpal tunnel syndrome or bios enosis. It's an area where there needs more education and more disease awareness. And we believe having more voices articulating how the disease manifests itself and helping the patients to get treated early is going to be key. One of the things we're doing, and I believe others will be doing as well, is to engage with a lot of centers to make sure that in electronic medical records, patients get flagged early. I think these are some of the initiatives that the industry is going to be making to make sure that those patients get quickly flagged. I don't know, Pushkal, do you have anything?

Yvonne L. Greenstreet: Tolga, I think another one for you.

Tolga Tanguler: Yeah, look, this is a disease, especially in the wild type cardiomyopathy patients don't start having these symptoms until sometimes it's too late, so that's one of the key drivers. The second thing is, there are only a few multidisciplinary centers. What we've seen is those multidisciplinary centers start expanding more and the awareness of how the disease actually manifests itself is being picked up by authority. As much as we say [inaudible] polyneuropathy, it's still a rare disease. The U.S has less than 200,000 patients. Therefore, it is not as common as what doctors used to see, cardiologists or neurologist or even in some cases, orthopedic surgeons where they see bilateral carpal tunnel syndrome or bios enosis. It's an area where there needs more education and more disease awareness. And we believe having more voices articulating how the disease manifests itself and helping the patients to get treated early is going to be key. One of the things we're doing, and I believe others will be doing as well, is to engage with a lot of centers to make sure that in electronic medical records, patients get flagged early. I think these are some of the initiatives that the industry is going to be making to make sure that those patients get quickly flagged. I don't know, Pushkal, do you have anything?

Pushkal Garg: Tolga, I think another one for you.

Yvonne Greenstreet: Tolga, I think another one for you.

Christine Lindenboom: Yeah. Look, this is a disease, especially in the wild-type cardiomyopathy. Patients don't start having these symptoms until sometimes it's too late. So that's one of the key drivers. The second thing is there are only few multidisciplinary centers. What we've seen is those multidisciplinary centers start expanding more. And the awareness of how disease actually manifests itself is being picked up by authorities. As much as we say it's tenfold of the polyneuropathy, it's still a rare disease. In the US, it's less than 200,000 patients. Therefore, it is not as common as what doctors used to see in cardiologists, or neurologists, or even, in some cases, orthopedic surgeons where they see bilateral carpal tunnel syndrome or spinal stenosis. It's an area where it needs more education, more disease awareness.

Tolga Tanguler: Yeah. Look, this is a disease, especially in the wild-type cardiomyopathy. Patients don't start having these symptoms until sometimes it's too late. So that's one of the key drivers. The second thing is there are only few multidisciplinary centers. What we've seen is those multidisciplinary centers start expanding more. And the awareness of how disease actually manifests itself is being picked up by authorities. As much as we say it's tenfold of the polyneuropathy, it's still a rare disease. In the US, it's less than 200,000 patients. Therefore, it is not as common as what doctors used to see in cardiologists, or neurologists, or even, in some cases, orthopedic surgeons where they see bilateral carpal tunnel syndrome or spinal stenosis. It's an area where it needs more education, more disease awareness.

Jeff: until sometimes it's too late. So that's one of the key drivers. The second thing is...

Jeff: There are only a few multidisciplinary centers, what we've seen is those multidisciplinary centers start expanding more, and the awareness of how disease actually manifests itself

Speaker Change: It's an area where...

Christine Lindenboom: We believe having more voices articulating how disease manifests itself and help the patients to get treated early is going to be key. One of the things we're doing, and I believe others will be doing as well, is to engage with a lot of centers to make sure that on electronic medical records, patients get start flagged early. I think these are some of the initiatives that the industry is going to be making to make sure those patients get quickly flagged. I don't know, Pushkal, do you have anything?

Tolga Tanguler: We believe having more voices articulating how disease manifests itself and help the patients to get treated early is going to be key. One of the things we're doing, and I believe others will be doing as well, is to engage with a lot of centers to make sure that on electronic medical records, patients get start flagged early. I think these are some of the initiatives that the industry is going to be making to make sure those patients get quickly flagged. I don't know, Pushkal, do you have anything?

Speaker Change: needs more education, more disease awareness and we believe having more voices

Speaker Change: Articulating how disease manifests itself and help the patients to get Treated early is going to be key one of the things we're doing and I believe others will be doing as well is to engage with a lot of

Speaker Change: Patients get start lagged?

Speaker Change: Early.

Pushkal: I think these are some of the initiatives that the industry is going to be making to make sure those patients get quickly flagged. I don't know, Pushkal, do you have anything? Yeah, no, Tolga, you said it very well. I mean, I think the only things I would just add is just a reminder that, you know, until about five years ago, there was no therapy.

Pushkal Garg: Yeah, no, Tolga, you said it very well. I mean, I think the only thing I would just add is just a reminder that until five years ago, there was no therapy for these patients at all that was specific, right? And so they were treated as sort of heart failure with preserved ejection fraction. And I think, to Tolga's point, now we have a therapy, and hopefully soon, multiple therapies for these patients. We've now, in just the last few years, had the proliferation of non-invasive diagnostic methods to identify these patients. And we're starting to understand more how to identify these patients based on red flag symptoms, such as polyneuropathy or spinal stenosis or carpal tunnel syndrome, things like that.

Pushkal Garg: Yeah, no, Tolga, you said it very well. I mean, I think the only things I would just add is just a reminder that until about 5 years ago, there was no therapy for these patients at all that was specific, right? And so they were treated as sort of heart failure with preserved ejection fraction. And I think to Tolga's point, now we have a therapy, hopefully soon multiple therapies for these patients. We've now, over just the last few years, had the proliferation of non-invasive diagnostic methods to identify these patients. And we're starting to understand more where how to identify these patients based on red flag symptoms such as polyneuropathy, spinal stenosis, or carpal tunnel syndrome, things like that.

Tolga: To Toga's point, now we have a therapy, hopefully soon multiple therapies for these patients. We've now, over just the last few years, had the proliferation of non-invasive diagnostic methods to identify these patients.

Pushkal Garg: We've now, in just the last few years, had the proliferation of non-invasive diagnostic methods to identify these patients. And we're starting to understand more how to identify these patients based on red flag symptoms, such as polyneuropathy or spinal stenosis or carpal tunnel syndrome, things like that.

Pushkal Garg: So I think there is just a heavy, heavy need for more disease education and awareness because we now have, we believe, hopefully multiple therapies for these patients that can actually stem the progression of this otherwise progressive and fatal disease. So I think there is a lot of growth here in terms of patients to treat. Helpful. Thank you.

So I think there is just a heavy, heavy need for more disease education and awareness because we now have, we believe, hopefully multiple therapies for these patients that can actually stem the progression of this otherwise progressive and fatal disease. So I think there is a lot of growth here in terms of patients to treat.

Pushkal Garg: So I think there is just a heavy, heavy need for more disease education awareness because we now have, we believe, hopefully multiple therapies for these patients that can actually stem the progression of this otherwise progressive and fatal disease. So I think there is a lot of growth here in terms of patients to treat.

[Analyst] (Jefferies LLC): Helpful. Thank you.

Mike Ulz: Helpful. Thank you.

Operator: Thank you. We'll take our next question from William Pickering with Bernstein. Your line is open.

William Pickering: Yes, hi, thank you so much for taking my question and congrats on the great results. Looking ahead to ESC, there seems to be a lot of investor interest in comparing the VUTRI monotherapy arm with the TAF plus placebo arm. Could you talk about the extent to which you think that is a helpful comparison and any limitations relative to just looking at VUTRI plus placebo versus placebo in the background TAF subgroup? Thank you.

[Analyst] (Bernstein): Yes. Hi. Thank you so much for taking my question and congrats on the great results. Looking ahead to ESC, there seems to be a lot of investor interest in comparing the VUTRI monotherapy arm with the TAF plus placebo arm. Could you talk about the extent to which you think that is a helpful comparison and any limitations relative to just looking at VUTRI versus placebo and the background TAF subgroup? Thank you.

William Pickering: Yes. Hi. Thank you so much for taking my question and congrats on the great results. Looking ahead to ESC, there seems to be a lot of investor interest in comparing the VUTRI monotherapy arm with the TAF plus placebo arm. Could you talk about the extent to which you think that is a helpful comparison and any limitations relative to just looking at VUTRI versus placebo and the background TAF subgroup? Thank you.

Speaker Change: The Vutri monotherapy arm with the TAP plus placebo arm, could you talk about the extent to which you think that is a helpful comparison and any limitations relative to just looking at Vutri plus Vutri versus placebo in the background TAP subgroup? Thank you.

Jeffrey Poulton: Yeah, thanks Will. Look, I think what we have here with Helios B is really a very, very rich study, right? This was a study done on 655 patients in the modern era. These were patients who were diagnosed with non-invasive means, as we've talked about, and we'll share more at ESC, it was a pretty rigorous test. These were patients, 40% who were already on an effective therapy, a good proportion of the monotherapy arm who started another effective therapy. In the midst of the study, patients started SGLT2s, other things. So it was a pretty rigorous test, and the results, we believe, are very, very encouraging.

Pushkal Garg: Yeah, thanks, Will. Look, I think what we have here with HELIOS-B is really a very, very rich study, right? This was a study done in 655 patients in the modern era. These were patients who were diagnosed with non-invasive means, as we've talked about, and we'll share more at ESC. It was a pretty rigorous test. These were patients, 40% who were already on an effective therapy, a good proportion of the monotherapy arm who started another effective therapy. In the midst of the study, patients started SGLT2s, other things. So it was a pretty rigorous test, and the results we believe are very, very encouraging. The one thing this study was not was a head-to-head study with tafamidis. That is the one thing it was not. It was not designed for that purpose. So the comparison that you're referring to really is a non-randomized comparison.

Speaker Change: Yeah, thanks, Will. Look, I think what we have here with HealSB is

Unknown Executive: These were patients, 40% who were already on an effective therapy, a good proportion of the monotherapy arm who started another effective therapy. In the midst of the study, patients started SGLT2s, other things. So it was a pretty rigorous test, and the results, we believe, are very, very encouraging. The one thing this study was not was a head-to-head study with [inaudible]. That is the one thing it was not. It was not designed for that purpose.

These were patients, 40% who were already on an effective therapy, a good proportion of the monotherapy arm who started another effective therapy. In the midst of the study, patients started SGLT2s, other things. So it was a pretty rigorous test, and the results, we believe, are very, very encouraging.

Tolga: with non-invasive means.

Tolga: As we've talked about and we'll share more at ESC.

Tolga: It was a pretty rigorous test. These were patients, 40% who were already on an effective therapy, a good proportion of monotherapy arm who started another effective therapy. In the midst of the study, patients started SGLT2s.

The one thing this study was not was a head-to-head study with [inaudible]. That is the one thing it was not. It was not designed for that purpose. And so the comparison that you're referring to really is a non-randomized comparison. And as you can imagine, the patients who entered in on TAF were different because they'd been on the drug for a while. Obviously, there were geographic differences among those patients. The majority of the TAF patients came from the U.S.

Unknown Executive: And so the comparison that you're referring to really is a non-randomized comparison. And as you can imagine, the patients who entered in on TAF were different because they'd been on the drug for a while. Obviously, there were geographic differences among those patients. The majority of the TAF patients came from the U.S.

Speaker Change: That is the one thing it was not. It was not designed for that purpose. And so the comparison that you're referring to really is a non-randomized comparison.

Pushkal Garg: As you can imagine, the patients who entered in on TAF were different because they'd been on the drug for a while. Obviously, there were geographic differences in those patients. The majority of the TAF patients came from the US. Comparing that then to the vutrisiran patients who were on monotherapy, it's really, unfortunately, a flawed analysis. I think what we'll see, as we highlighted in the top-line results, is that vutrisiran appears to have really encouraging efficacy on every parameter we measured, both as a monotherapy and evidence of additive efficacy on top of tafamidis, and consistent results across the whole series of endpoints that we've looked at. Next question.

Speaker Change: Obviously, there were geographic differences in those patients, the majority of the TAP patients came from the U.S., you know, so comparing that then to the Boutry patients who were on monotherapy, it's really unfortunately a flawed analysis.

Unknown Executive: So comparing that, then, to the VUTRI patients who were on monotherapy, it's really, unfortunately, a flawed analysis. I think what we'll see, as we highlighted in the top-line results, is that VUTRI appears to have really encouraging efficacy on every parameter we measured, both as a monotherapy and evidence of additive efficacy on top of [inaudible] and consistent results across the whole series of endpoints that we looked at. Next question. We'll take our next question from Miles Wynter with William Blair, your line is open. Hey, thanks for taking the question. Just with ISA releasing their draft guidance on TTRCM pricing, I know that was in relevance to [inaudible], but there's also some commentary about VUTRISIRAN in that as well.

So comparing that, then, to the VUTRI patients who were on monotherapy, it's really, unfortunately, a flawed analysis. I think what we'll see, as we highlighted in the top-line results, is that VUTRI appears to have really encouraging efficacy on every parameter we measured, both as a monotherapy and evidence of additive efficacy on top of [inaudible] and consistent results across the whole series of endpoints that we looked at. Next question. We'll take our next question from Miles Wynter with William Blair, your line is open.

I think what we'll see as we highlight it in the top line results is

Speaker Change: that Boutry

Yvonne L. Greenstreet: Next question.

Operator: We'll take our next question from Miles Wynter with William Blair. Your line is open.

William Blair: Hey, thanks for taking the question. Just with ISA releasing their draft guidance on TTRCM pricing, I know that was in relevance to [inaudible], but there's also some commentary about VUTRISIRAN in that as well. Is Alnylam intending to be at that public hearing on September 20, and if so, are you going to be presenting [inaudible]?

Operator: Thank you. We'll take our next question from Miles Minter with William Blair. Your line is open.

Unknown Executive: Is Alnylam intending to be at that public hearing on September 20, and if so, are you going to be presenting [inaudible]? Yeah, thank you for that question. As ISA, I think, noted, they made this assessment prior to our disclosure of Helios B top-line results, and therefore, it wasn't a complete analysis. We remain engaged with any health outcomes authority, and we'll continue to engage with ISA and others. We haven't disclosed whether we will be part of the hearing.

Is Alnylam intending to be at that public hearing on September 20, and if so, are you going to be presenting [inaudible]?

[Analyst] (William Blair): Hey, thanks for taking the question. Just with us relating that draft guidance on TTR-CM pricing, I know that was irrelevant to tafamidis, but there's also some commentary about vutrisiran in that as well. Is Alnylam intending to be at that public hearing in September 20, and if you are, are you going to be presenting something on cost-effectiveness of vutrisiran and TTR-CM? Thanks very much.

Myles Minter: Hey, thanks for taking the question. Just with us relating that draft guidance on TTR-CM pricing, I know that was irrelevant to tafamidis, but there's also some commentary about vutrisiran in that as well. Is Alnylam intending to be at that public hearing in September 20, and if you are, are you going to be presenting something on cost-effectiveness of vutrisiran and TTR-CM? Thanks very much.

Hey, thanks for taking the question. Just with ISA releasing their draft guidance on TTRCM pricing, I know that was in relevance to defamitists, but there's also some commentary about Futrisaran in that as well. Is Alnylam intending to be at that public hearing in September 20, and if you are, are you going to be presenting something on cost-effectiveness?

Tolga Tanguler: Yeah, thank you for that question. As ISA, I think, noted, they made this assessment prior to our disclosure of Helios B top-line results, and therefore, it wasn't a complete analysis. We remain engaged with any health outcomes authority, and we'll continue to engage with ISA and others. We haven't disclosed whether we will be part of the hearing.

Christine Lindenboom: Yeah. Thank you for that question. As ISA, I think, noted, they made this assessment prior to our disclosure of HELIOS-B top-line results, and therefore, it wasn't a complete analysis. We remain engaged with any health outcomes authority and will continue to engage with ISA and others. We haven't disclosed whether we would be part of the hearing.

Tolga Tanguler: Yeah. Thank you for that question. As ISA, I think, noted, they made this assessment prior to our disclosure of HELIOS-B top-line results, and therefore, it wasn't a complete analysis. We remain engaged with any health outcomes authority and will continue to engage with ISA and others. We haven't disclosed whether we would be part of the hearing.

and PTRCM. Thanks very much.

Speaker Change: They made this assessment prior to our disclosure of Helios V top-line results and therefore...

It was in a complete analysis.

Christine Regan Lindenboom: Okay, I think we have time for one more question. The last question, please. Yes, that last question will come from Luca Issi with RBC Capital. Your line is open. Oh, great. Thank you so much for squeezing me in. Congratulations on all the progress. Maybe circling back on Gena's question here, Pushkal, for TTR SC04, which is obviously super important as we think about the royalty to Santa Fe on phase three, do you basically need to run another Helios B, or can you maybe get away with a smaller PK-PD trial? And maybe related, what's the dose that you're going to pursue? I think in the STAT portion of the trial, you went all the way to 600 milligrams, so I was wondering if that is the go-forward dose.

Okay, I think we have time for one more question. The last question, please. Yes, that last question will come from Luca Issi with RBC Capital. Your line is open.

Yvonne L. Greenstreet: Okay, I think we have time for one more question. The last question, please.

Pushkal Garg: Okay. I think we have time for one more question. The last question, please.

Yvonne Greenstreet: Okay. I think we have time for one more question. The last question, please.

Speaker Change: Okay, I think we have time for one more question.

Operator: Yes, that last question will come from Luca Issi with RBC Capital. Your line is open.

Luca Issi: Oh, great. Thank you so much for squeezing me in. Congratulations on all the progress. Maybe circling back on Gena's question here, Pushkal, for TTR SC04, which is obviously super important as we think about the royalty to Santa Fe on phase three, do you basically need to run another Helios B, or can you maybe get away with a smaller PK-PD trial? And maybe related, what's the dose that you're going to pursue? I think in the STAT portion of the trial, you went all the way to 600 milligrams, so I was wondering if that is the go-forward dose. Thanks so much.

[Analyst] (RBC Capital Markets): Oh, great. Thanks so much for squeezing me in. Congrats on all the progress. Maybe circling back on Gina's question here, Pushkal, for TTR-SC04, which is obviously super important as we think about the royalty to Sanofi on the phase 3. Do you basically need to run another Helios V, or you can maybe get away with a smaller PKPD trial? And maybe related, what's the dose that you're going to pursue? I think the SAD portion of the trial, you went all the way to 600mg. So just wondering if that is the go-forward dose. Thanks so much.

Luca Issi: Oh, great. Thanks so much for squeezing me in. Congrats on all the progress. Maybe circling back on Gina's question here, Pushkal, for TTR-SC04, which is obviously super important as we think about the royalty to Sanofi on the phase 3. Do you basically need to run another Helios V, or you can maybe get away with a smaller PKPD trial? And maybe related, what's the dose that you're going to pursue? I think the SAD portion of the trial, you went all the way to 600mg. So just wondering if that is the go-forward dose. Thanks so much.

Do you basically need to run another Heliospeed or you can maybe get away with a smaller PKPD trial?

And maybe related, what's the dose that you're going to pursue? I think the SAD portion of the trial, you went all the way to 600 milligrams, so just wondering if that is the go-forward dose. Thanks so much.

Christine Lindenboom: Okay. Well, we're going to come back to that question because, as I said, we're not ready really to get into details of what the next detailed step is in our clinical plan. So we'll come back and share more on that later. But thanks for your interest. We're also very excited about the program. Thanks, Luca.

Yvonne Greenstreet: Okay. Well, we're going to come back to that question because, as I said, we're not ready really to get into details of what the next detailed step is in our clinical plan. So we'll come back and share more on that later. But thanks for your interest. We're also very excited about the program. Thanks, Luca.

Unknown Executive: Okay, well, we're going to come back to that question, because I said we're not ready, really, to get into the details of what the next detailed step is in our clinical plan. So we'll come back and share more on that later, but thanks for your interest. We're also very excited about the program. Thanks Luca. Okay, I think that brings our call to a close. I just want to thank everybody for joining. Really the second quarter of 2024 marks an inflection point in Alnylam's journey and we really are proud of our progress. Tolga has described delivering robust commercial growth, Pushkal has gone through some of the incredible advancements in our pipeline. Now more than ever, we believe that we are firmly on a path to becoming a top tier biotech company. Thank you everybody and have a great day.

Yvonne L. Greenstreet: Okay, well, we're going to come back to that question, because I said we're not ready, really, to get into the details of what the next detailed step is in our clinical plan. So we'll come back and share more on that later, but thanks for your interest. We're also very excited about the program. Thanks Luca.

Pushkal Garg: Okay. I think that brings our call to a close. Just want to thank everybody for joining. I mean, really, Q2 2024 has marked an inflection point in Alnylam's journey, and we really are proud of our progress. As Tolga describes, they're living robust commercial growth. Pushkal has gone through some of the incredible advancements in our pipeline. Now more than ever, we believe that we're firmly on a path to becoming a top-tier biotech company. Thank you, everybody, and have a great day.

Yvonne Greenstreet: Okay. I think that brings our call to a close. Just want to thank everybody for joining. I mean, really, Q2 2024 has marked an inflection point in Alnylam's journey, and we really are proud of our progress. As Tolga describes, they're living robust commercial growth. Pushkal has gone through some of the incredible advancements in our pipeline. Now more than ever, we believe that we're firmly on a path to becoming a top-tier biotech company. Thank you, everybody, and have a great day.

Okay, I think that brings our call to a close. I just want to thank everybody for joining. Really the second quarter of 2024 marks an inflection point in Alnylam's journey and we really are proud of our progress. Tolga has described delivering robust commercial growth, Pushkal has gone through some of the incredible advancements in our pipeline. Now more than ever, we believe that we are firmly on a path to becoming a top tier biotech company. Thank you everybody and have a great day.

Thanks, Luca.

Operator: Thank you. This does conclude today's program. Thank you for your participation. You may disconnect at any time.

[inaudible]

Q2 2024 Alnylam Pharmaceuticals Inc Earnings Call

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